Vujnović, Ivana

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orcid::0000-0001-8201-2459
  • Vujnović, Ivana (18)
  • Prijić, Ivana (10)
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Author's Bibliography

Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development

Petrušić, Marija; Stojić-Vukanić, Zorica; Pilipović, Ivan; Kosec, Duško; Prijić, Ivana; Leposavić, Gordana

(Elsevier, 2023)

TY  - JOUR
AU  - Petrušić, Marija
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Prijić, Ivana
AU  - Leposavić, Gordana
PY  - 2023
UR  - http://intor.torlakinstitut.com/handle/123456789/633
AB  - The study was aimed to examine putative contribution of thymic involution to ageing-associated increase in susceptibility of Albino Oxford (AO) rats to the development of clinical EAE, and vice versa influence of the disease on the progression of thymic involution. To this end we examined (i) the parameters of thymocyte negative selection efficacy, the thymic generation of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and thymic capacity to instruct/predetermine IL-17-producing T-cell differentiation, and thymopietic efficacy-associated accumulation of “inflammescent” cytotoxic CD28- T cells in the periphery, and (ii) the key underlying mechanisms in young and old non-immunised AO rats and their counterparts immunised for EAE (on the 16th day post-immunisation when the disease in old rats reached the plateau) using flow cytometry analysis and/or RT-qPCR. It was found that thymic involution impairs: (i) the efficacy of negative selection (by affecting thymocyte expression of CD90, negative regulator of selection threshold and the expression of thymic stromal cell integrity factors) and (ii) Treg generation (by diminishing expression of cytokines supporting their differentiation/maturation). Additionally, the results suggest that thymic involution facilitates CD8+ T-cell differentiation into IL-17-producing cells (previously linked to the development of clinical EAE in old AO rats). Furthermore, they confirmed that ageing-related decrease in thymic T-cell output (as indicated by diminished frequency of recent thymic emigrants in peripheral blood) resulted in the accumulation of CD28- T cells in peripheral blood and, upon immunisation, in the target organ. On the other hand, the development of EAE (most likely by increasing circulatory levels of proinflammatory cytokines) contributed to the decline in thymic output of T cells, including Tregs, and thereby to the progression/maintenance of clinical EAE. Thus, in AO rats thymic involution via multi-layered mechanisms may favour the development of clinically manifested autoimmunity, which, in turn, precipitates the thymus atrophy.
PB  - Elsevier
T2  - Experimental Gerontology
T1  - Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development
SP  - 112009
VL  - 171
DO  - 10.1016/j.exger.2022.112009
ER  - 
@article{
author = "Petrušić, Marija and Stojić-Vukanić, Zorica and Pilipović, Ivan and Kosec, Duško and Prijić, Ivana and Leposavić, Gordana",
year = "2023",
abstract = "The study was aimed to examine putative contribution of thymic involution to ageing-associated increase in susceptibility of Albino Oxford (AO) rats to the development of clinical EAE, and vice versa influence of the disease on the progression of thymic involution. To this end we examined (i) the parameters of thymocyte negative selection efficacy, the thymic generation of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and thymic capacity to instruct/predetermine IL-17-producing T-cell differentiation, and thymopietic efficacy-associated accumulation of “inflammescent” cytotoxic CD28- T cells in the periphery, and (ii) the key underlying mechanisms in young and old non-immunised AO rats and their counterparts immunised for EAE (on the 16th day post-immunisation when the disease in old rats reached the plateau) using flow cytometry analysis and/or RT-qPCR. It was found that thymic involution impairs: (i) the efficacy of negative selection (by affecting thymocyte expression of CD90, negative regulator of selection threshold and the expression of thymic stromal cell integrity factors) and (ii) Treg generation (by diminishing expression of cytokines supporting their differentiation/maturation). Additionally, the results suggest that thymic involution facilitates CD8+ T-cell differentiation into IL-17-producing cells (previously linked to the development of clinical EAE in old AO rats). Furthermore, they confirmed that ageing-related decrease in thymic T-cell output (as indicated by diminished frequency of recent thymic emigrants in peripheral blood) resulted in the accumulation of CD28- T cells in peripheral blood and, upon immunisation, in the target organ. On the other hand, the development of EAE (most likely by increasing circulatory levels of proinflammatory cytokines) contributed to the decline in thymic output of T cells, including Tregs, and thereby to the progression/maintenance of clinical EAE. Thus, in AO rats thymic involution via multi-layered mechanisms may favour the development of clinically manifested autoimmunity, which, in turn, precipitates the thymus atrophy.",
publisher = "Elsevier",
journal = "Experimental Gerontology",
title = "Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development",
pages = "112009",
volume = "171",
doi = "10.1016/j.exger.2022.112009"
}
Petrušić, M., Stojić-Vukanić, Z., Pilipović, I., Kosec, D., Prijić, I.,& Leposavić, G.. (2023). Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development. in Experimental Gerontology
Elsevier., 171, 112009.
https://doi.org/10.1016/j.exger.2022.112009
Petrušić M, Stojić-Vukanić Z, Pilipović I, Kosec D, Prijić I, Leposavić G. Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development. in Experimental Gerontology. 2023;171:112009.
doi:10.1016/j.exger.2022.112009 .
Petrušić, Marija, Stojić-Vukanić, Zorica, Pilipović, Ivan, Kosec, Duško, Prijić, Ivana, Leposavić, Gordana, "Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development" in Experimental Gerontology, 171 (2023):112009,
https://doi.org/10.1016/j.exger.2022.112009 . .
2
2

Supplementary information for the article: Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Jasnić, Nebojša; Đorđević, Jelena; Leposavić, Gordana

(Springer, 2022)

TY  - DATA
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/649
PB  - Springer
T2  - Cellular and Molecular Neurobiology
T1  - Supplementary information for the article:
Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor
Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual
Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular
and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z
UR  - https://hdl.handle.net/21.15107/rcub_intor_649
ER  - 
@misc{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Jasnić, Nebojša and Đorđević, Jelena and Leposavić, Gordana",
year = "2022",
publisher = "Springer",
journal = "Cellular and Molecular Neurobiology",
title = "Supplementary information for the article:
Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor
Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual
Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular
and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z",
url = "https://hdl.handle.net/21.15107/rcub_intor_649"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnić, N., Đorđević, J.,& Leposavić, G.. (2022). Supplementary information for the article:
Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor
Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual
Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular
and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z. in Cellular and Molecular Neurobiology
Springer..
https://hdl.handle.net/21.15107/rcub_intor_649
Pilipović I, Stojić-Vukanić Z, Prijić I, Jasnić N, Đorđević J, Leposavić G. Supplementary information for the article:
Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor
Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual
Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular
and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z. in Cellular and Molecular Neurobiology. 2022;.
https://hdl.handle.net/21.15107/rcub_intor_649 .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Jasnić, Nebojša, Đorđević, Jelena, Leposavić, Gordana, "Supplementary information for the article:
Pilipović, I.; Stojić-Vukanić, Z.; Prijić, I.; Jasnić, N.; Đorđević, J.; Leposavić, G. β-Adrenoceptor
Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual
Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. Cellular
and Molecular Neurobiology 2022. https://doi.org/10.1007/s10571-022-01246-z" in Cellular and Molecular Neurobiology (2022),
https://hdl.handle.net/21.15107/rcub_intor_649 .

β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Jasnić, Nebojša; Đorđević, Jelena; Leposavić, Gordana

(Springer, 2022)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4198
UR  - http://intor.torlakinstitut.com/handle/123456789/622
AB  - Our previous studies showed more severe experimental autoimmune encephalomyelitis (EAE) in male compared with female adult rats, and moderating effect of propranolol-induced β-adrenoceptor blockade on EAE in females, the effect associated with transcriptional stimulation of Nrf2/HO-1 axis in spinal cord microglia. This study examined putative sexual dimor- phism in propranolol action on EAE severity. Propranolol treatment beginning from the onset of clinical EAE mitigated EAE severity in rats of both sexes, but to a greater extent in males exhibiting higher noradrenaline levels and myeloid cell β 2 -adrenoceptor expression in spinal cord. This correlated with more prominent stimulatory effects of propranolol not only on CX3CL1/CX3CR1/Nrf2/HO-1 cascade, but also on Stat3/Socs3 signaling axis in spinal cord microglia/myeloid cells (mirrored in the decreased Stat3 and the increased Socs3 expression) from male rats compared with their female counterparts. Propranolol diminished the frequency of activated cells among microglia, increased their phagocyting/endocyting capacity, and shifted cytokine secretory profile of microglia/blood-borne myeloid cells towards an anti-inflammatory/neuroprotective phenotype. Additionally, it downregulated the expression of chemokines (CCL2, CCL19/21) driving T-cell/monocyte traf- ficking into spinal cord. Consequently, in propranolol-treated rats fewer activated CD4+ T cells and IL-17+ T cells, including CD4+IL17+ cells coexpressing IFN-γ/GM-CSF, were recovered from spinal cord of propranolol-treated rats compared with sex-matched saline-injected controls. All the effects of propranolol were more prominent in males. The study as a whole disclosed that sexual dimorphism in multiple molecular mechanisms implicated in EAE development may be responsible for greater severity of EAE in male rats and sexually dimorphic action of substances affecting them.
PB  - Springer
T2  - Cellular and Molecular Neurobiology
T1  - β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males
DO  - 10.1007/s10571-022-01246-z
ER  - 
@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Jasnić, Nebojša and Đorđević, Jelena and Leposavić, Gordana",
year = "2022",
abstract = "Our previous studies showed more severe experimental autoimmune encephalomyelitis (EAE) in male compared with female adult rats, and moderating effect of propranolol-induced β-adrenoceptor blockade on EAE in females, the effect associated with transcriptional stimulation of Nrf2/HO-1 axis in spinal cord microglia. This study examined putative sexual dimor- phism in propranolol action on EAE severity. Propranolol treatment beginning from the onset of clinical EAE mitigated EAE severity in rats of both sexes, but to a greater extent in males exhibiting higher noradrenaline levels and myeloid cell β 2 -adrenoceptor expression in spinal cord. This correlated with more prominent stimulatory effects of propranolol not only on CX3CL1/CX3CR1/Nrf2/HO-1 cascade, but also on Stat3/Socs3 signaling axis in spinal cord microglia/myeloid cells (mirrored in the decreased Stat3 and the increased Socs3 expression) from male rats compared with their female counterparts. Propranolol diminished the frequency of activated cells among microglia, increased their phagocyting/endocyting capacity, and shifted cytokine secretory profile of microglia/blood-borne myeloid cells towards an anti-inflammatory/neuroprotective phenotype. Additionally, it downregulated the expression of chemokines (CCL2, CCL19/21) driving T-cell/monocyte traf- ficking into spinal cord. Consequently, in propranolol-treated rats fewer activated CD4+ T cells and IL-17+ T cells, including CD4+IL17+ cells coexpressing IFN-γ/GM-CSF, were recovered from spinal cord of propranolol-treated rats compared with sex-matched saline-injected controls. All the effects of propranolol were more prominent in males. The study as a whole disclosed that sexual dimorphism in multiple molecular mechanisms implicated in EAE development may be responsible for greater severity of EAE in male rats and sexually dimorphic action of substances affecting them.",
publisher = "Springer",
journal = "Cellular and Molecular Neurobiology",
title = "β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males",
doi = "10.1007/s10571-022-01246-z"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnić, N., Đorđević, J.,& Leposavić, G.. (2022). β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. in Cellular and Molecular Neurobiology
Springer..
https://doi.org/10.1007/s10571-022-01246-z
Pilipović I, Stojić-Vukanić Z, Prijić I, Jasnić N, Đorđević J, Leposavić G. β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males. in Cellular and Molecular Neurobiology. 2022;.
doi:10.1007/s10571-022-01246-z .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Jasnić, Nebojša, Đorđević, Jelena, Leposavić, Gordana, "β-Adrenoceptor Blockade Moderates Neuroinflammation in Male and Female EAE Rats and Abrogates Sexual Dimorphisms in the Major Neuroinflammatory Pathways by Being More Efficient in Males" in Cellular and Molecular Neurobiology (2022),
https://doi.org/10.1007/s10571-022-01246-z . .
3
2

Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Leposavić, Gordana

(Frontiers Media Sa, Lausanne, 2020)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/571
AB  - The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through beta(2)-adrenoceptor, a role for alpha-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Endocrinology
T1  - Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis
VL  - 10
DO  - 10.3389/fendo.2019.00921
ER  - 
@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Leposavić, Gordana",
year = "2020",
abstract = "The role of stress effector systems in the initiation and progression of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, has strongly been suggested. To corroborate this notion, alterations in activity of the sympathoadrenal and sympathoneural axes of sympathoadrenal system (a major communication pathway between the central nervous system and the immune system), mirrored in altered release of their end-point mediators (adrenaline and noradrenaline, respectively), are shown to precede (in MS) and/or occur during development of MS and EAE in response to immune cell activation (in early phase of disease) and disease-related damage of sympathoadrenal system neurons and their projections (in late phase of disease). To add to the complexity, innate immunity cells and T-lymphocytes synthesize noradrenaline that may be implicated in a local autocrine/paracrine self-amplifying feed-forward loop to enhance myeloid-cell synthesis of proinflammatory cytokines and inflammatory injury. Furthermore, experimental manipulations targeting noradrenaline/adrenaline action are shown to influence clinical outcome of EAE, in a disease phase-specific manner. This is partly related to the fact that virtually all types of cells involved in the instigation and progression of autoimmune inflammation and target tissue damage in EAE/MS express functional adrenoceptors. Although catecholamines exert majority of immunomodulatory effects through beta(2)-adrenoceptor, a role for alpha-adrenoceptors in EAE pathogenesis has also been indicated. In this review, we summarize all aforementioned aspects of immunopathogenetic action of catecholamines in EAE/MS as possibly important for designing new strategies targeting their action to prevent/mitigate autoimmune neuroinflammation and tissue damage.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Endocrinology",
title = "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis",
volume = "10",
doi = "10.3389/fendo.2019.00921"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I.,& Leposavić, G.. (2020). Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology
Frontiers Media Sa, Lausanne., 10.
https://doi.org/10.3389/fendo.2019.00921
Pilipović I, Stojić-Vukanić Z, Prijić I, Leposavić G. Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. in Frontiers in Endocrinology. 2020;10.
doi:10.3389/fendo.2019.00921 .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Leposavić, Gordana, "Role of the End-Point Mediators of Sympathoadrenal and Sympathoneural Stress Axes in the Pathogenesis of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis" in Frontiers in Endocrinology, 10 (2020),
https://doi.org/10.3389/fendo.2019.00921 . .
2
4
1
4

Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia

Pilipović, Ivan; Stojić-Vukanić, Zorica; Prijić, Ivana; Jasnić, Nebojša; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2020)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Prijić, Ivana
AU  - Jasnić, Nebojša
AU  - Leposavić, Gordana
PY  - 2020
UR  - http://intor.torlakinstitut.com/handle/123456789/561
AB  - Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and up regulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1 beta and IL-23, and possibly IL-6, followed by increased proportion of IL-10 expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4 + T cells, as well as CD4 + T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17 + cells co-producing IFN-gamma and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through beta-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests beta-adrenoceptor-mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Neurobiology of Disease
T1  - Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia
VL  - 134
DO  - 10.1016/j.nbd.2019.104665
ER  - 
@article{
author = "Pilipović, Ivan and Stojić-Vukanić, Zorica and Prijić, Ivana and Jasnić, Nebojša and Leposavić, Gordana",
year = "2020",
abstract = "Sympathetic dysfunction is suggested to contribute to development of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) alike. Considering important role of microglia in development/resolution of neuroinflammation, contribution of noradrenaline, the key sympathetic end-point mediator, in modulation of microglial phenotypic and functional properties in rat EAE model was examined. The study showed that noradrenaline acting in neurocrine and autocrine/paracrine way might influence microglia during EAE. Propranolol treatment over the effector phase moderated EAE course. This was associated with the increased proportion of microglia expressing CX3CR1, the key molecule in their immunomodulatory/neuroprotective action, and up regulation of CX3CR1 downstream Nrf2 gene. This correlated with the increased heme oxygenase-1 (HO-1) expression and phagocytic capacity of microglia, and their phenotypic changes mirrored in increased proportion of CD163- and CD83-expressing cells. The enhanced HO-1 expression was linked with the decreased proportion of microglial cells expressing IL-1 beta and IL-23, and possibly IL-6, followed by increased proportion of IL-10 expressing microglia, and downregulated MCP-1/CCL2 expression. Consistently, spinal cord infiltration with blood-borne myeloid and CD4 + T cells, as well as CD4 + T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17 + cells co-producing IFN-gamma and GM-CSF were decreased in propranolol-treated rats compared with saline-injected controls. The in vitro investigations of the effects of noradrenaline on microglia showed that noradrenaline through beta-adrenoceptor may influence Nrf2 expression also via CX3CR1-independent route. The study suggests beta-adrenoceptor-mediated neuroinflammation-promoting role of noradrenaline in EAE via modulation of microglial Nrf2 expression, and thereby forms the basis for further translational pharmacological research to improve multiple sclerosis therapy.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Neurobiology of Disease",
title = "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia",
volume = "134",
doi = "10.1016/j.nbd.2019.104665"
}
Pilipović, I., Stojić-Vukanić, Z., Prijić, I., Jasnić, N.,& Leposavić, G.. (2020). Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease
Academic Press Inc Elsevier Science, San Diego., 134.
https://doi.org/10.1016/j.nbd.2019.104665
Pilipović I, Stojić-Vukanić Z, Prijić I, Jasnić N, Leposavić G. Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia. in Neurobiology of Disease. 2020;134.
doi:10.1016/j.nbd.2019.104665 .
Pilipović, Ivan, Stojić-Vukanić, Zorica, Prijić, Ivana, Jasnić, Nebojša, Leposavić, Gordana, "Propranolol diminished severity of rat EAE by enhancing immunoregulatory/protective properties of spinal cord microglia" in Neurobiology of Disease, 134 (2020),
https://doi.org/10.1016/j.nbd.2019.104665 . .
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Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia

Pilipović, Ivan; Prijić, Ivana; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, 2019)

TY  - CONF
AU  - Pilipović, Ivan
AU  - Prijić, Ivana
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/854
AB  - Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with findings indicating that noradrenaline, the key sympathetic end-point mediator, through β- adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β- adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol over the effector phase of EAE substantially moderated neurological symptoms of the disease. This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological study examining influence of noradrenaline/propranolol on functional properties of microglia showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol- administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-y and GM-CSF. The study suggests a neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor– mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for future translational pharmacological research to optimize multiple sclerosis therapy.
PB  - Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade
PB  - Immunological Society of Serbia
C3  - Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
T1  - Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia
EP  - 69
SP  - 69
UR  - https://hdl.handle.net/21.15107/rcub_intor_854
ER  - 
@conference{
author = "Pilipović, Ivan and Prijić, Ivana and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Sympathetic dysfunction was proposed to participate in development of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). This may be linked with findings indicating that noradrenaline, the key sympathetic end-point mediator, through β- adrenoceptor exerts immunomodulatory action. Considering importance of the target tissue for the clinical outcome of EAE, the study investigated the effects of propranolol, a non-selective β- adrenoceptor blocker, on the disease severity in Dark Agouti rats. Administration of propranolol over the effector phase of EAE substantially moderated neurological symptoms of the disease. This correlated with the increased proportion of spinal cord microglia expressing CX3CR1, the crucial neuroinflammation-limiting molecule, and upregulated expression of Nrf2, the key CX3CR1 downstream target gene. Additionally, in spinal cord of propranolol-administered rats the expression of heme-oxigenase 1, Nrf2 target gene, was upregulated. Consequently, microglia from propranolol-administered rats, exhibited increased proportion of IL-10–expressing cells, but decreased those of IL-1β– and IL-23–expressing ones. Propranolol also downregulated the IL-6 and MCP-1/CCL2 expression in spinal cord. Furthermore, propranolol affecting CXCR1/Nrf2 signaling pathway enhanced microglial phagocytic/endocytic capacity and surface expression of anti-inflammatory CD163/CD83 markers. Results from in vitro pharmacological study examining influence of noradrenaline/propranolol on functional properties of microglia showed that microglia synthesize noradrenaline, which, in turn, through β-adrenoceptor, downregulated their Nrf2 expression, in a CX3CR1-independent manner. In accordance with microglial shift towards a more anti-inflammatory profile, in spinal cord of propranolol- administered rats was found: i) decreased infiltration with blood-borne myeloid and CD4+ T cells, and ii) reduced CD4+ T-cell reactivation/proliferation and differentiation into highly pathogenic IL-17+ cells co-producing IFN-y and GM-CSF. The study suggests a neuroinflammation-promoting role for central noradrenaline in EAE, via β-adrenoceptor– mediated modulation of microglial Nrf2 expression. Thus, it points out to a putative target for future translational pharmacological research to optimize multiple sclerosis therapy.",
publisher = "Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Immunological Society of Serbia",
journal = "Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019",
title = "Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia",
pages = "69-69",
url = "https://hdl.handle.net/21.15107/rcub_intor_854"
}
Pilipović, I., Prijić, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019
Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade., 69-69.
https://hdl.handle.net/21.15107/rcub_intor_854
Pilipović I, Prijić I, Stojić-Vukanić Z, Leposavić G. Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia. in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019. 2019;:69-69.
https://hdl.handle.net/21.15107/rcub_intor_854 .
Pilipović, Ivan, Prijić, Ivana, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Propranolol reduced severity of eae by increasing the Expression of Nrf2 in microglia" in Immunology at the confluence of Multidisciplinary approaches, Abstract book, Hotel Mona plaza, Belgrade December 6th-8th, 2019 (2019):69-69,
https://hdl.handle.net/21.15107/rcub_intor_854 .

Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis

Pilipović, Ivan; Vujnović, Ivana; Petrović, Raisa; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Karger, Basel, 2019)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Petrović, Raisa
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/541
AB  - Objective: We examined the effect of beta-adrenoceptor (AR) blockade in the preclinical phase of experimental autoimmune encephalomyelitis (EAE), the most commonly used model of multiple sclerosis, on the development of primary CD4+ T-cell responses in draining lymph nodes (dLNs). Methods: CD11b+ cell migration to dLNs, CD4+ T-cell activation/proliferation, and IL-17+ CD4+ (Th17) cell numbers in dLN and spinal cord (SC) were examined in male and female Dark Agouti rats using flow cytometry analysis. Results: Irrespective of sex, in propranolol-treated (PT) rats, migration of CD11b+ antigen-presenting cells from the site of immunization to dLNs was impaired compared with saline-treated controls and consequently the frequency of all CD11b+ cells in dLNs and activated cells among them, too. This correlated with decreased expression of CCL19/21 transcripts in dLNs. Consistently, the frequency of activated/proliferating cells among dLN CD4+ T cells was reduced in PT rats. Additionally, propranolol reduced the number of Th17 cells in dLNs and SC. Consistently, male and female PT rats exhibited a decreased incidence of EAE and prolonged duration of the asymptomatic disease phase. Conclusion: This study suggests that sympathetic dysregulation is involved in the outbreak of clinical EAE. (C) 2019 S. Karger AG, Basel
PB  - Karger, Basel
T2  - Neuroimmunomodulation
T1  - Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis
EP  - 138
IS  - 3
SP  - 129
VL  - 26
DO  - 10.1159/000500094
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Petrović, Raisa and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2019",
abstract = "Objective: We examined the effect of beta-adrenoceptor (AR) blockade in the preclinical phase of experimental autoimmune encephalomyelitis (EAE), the most commonly used model of multiple sclerosis, on the development of primary CD4+ T-cell responses in draining lymph nodes (dLNs). Methods: CD11b+ cell migration to dLNs, CD4+ T-cell activation/proliferation, and IL-17+ CD4+ (Th17) cell numbers in dLN and spinal cord (SC) were examined in male and female Dark Agouti rats using flow cytometry analysis. Results: Irrespective of sex, in propranolol-treated (PT) rats, migration of CD11b+ antigen-presenting cells from the site of immunization to dLNs was impaired compared with saline-treated controls and consequently the frequency of all CD11b+ cells in dLNs and activated cells among them, too. This correlated with decreased expression of CCL19/21 transcripts in dLNs. Consistently, the frequency of activated/proliferating cells among dLN CD4+ T cells was reduced in PT rats. Additionally, propranolol reduced the number of Th17 cells in dLNs and SC. Consistently, male and female PT rats exhibited a decreased incidence of EAE and prolonged duration of the asymptomatic disease phase. Conclusion: This study suggests that sympathetic dysregulation is involved in the outbreak of clinical EAE. (C) 2019 S. Karger AG, Basel",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis",
pages = "138-129",
number = "3",
volume = "26",
doi = "10.1159/000500094"
}
Pilipović, I., Vujnović, I., Petrović, R., Stojić-Vukanić, Z.,& Leposavić, G.. (2019). Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis. in Neuroimmunomodulation
Karger, Basel., 26(3), 129-138.
https://doi.org/10.1159/000500094
Pilipović I, Vujnović I, Petrović R, Stojić-Vukanić Z, Leposavić G. Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis. in Neuroimmunomodulation. 2019;26(3):129-138.
doi:10.1159/000500094 .
Pilipović, Ivan, Vujnović, Ivana, Petrović, Raisa, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Propranolol Impairs Primary Immune Responses in Rat Experimental Autoimmune Encephalomyelitis" in Neuroimmunomodulation, 26, no. 3 (2019):129-138,
https://doi.org/10.1159/000500094 . .
6
3
6

Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?

Vujnović, Ivana; Pilipović, Ivan; Jasnić, Nebojša; Petrović, Raisa; Blagojević, Veljko; Arsenović-Ranin, Nevena; Stojić-Vukanić, Zorica; Đorđević, Jelena; Leposavić, Gordana

(Academic Press Inc Elsevier Science, San Diego, 2019)

TY  - JOUR
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Jasnić, Nebojša
AU  - Petrović, Raisa
AU  - Blagojević, Veljko
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Đorđević, Jelena
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/539
AB  - Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Cellular Immunology
T1  - Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?
EP  - 57
SP  - 48
VL  - 336
DO  - 10.1016/j.cellimm.2018.12.009
ER  - 
@article{
author = "Vujnović, Ivana and Pilipović, Ivan and Jasnić, Nebojša and Petrović, Raisa and Blagojević, Veljko and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Đorđević, Jelena and Leposavić, Gordana",
year = "2019",
abstract = "Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4 + T-cell (auto) immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (beta-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4 + T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of beta(2)-adrenoceptor-expressing CD4 + T lymphocytes and antigen presenting cells. Propranolol, irrespective of exogenous noradrenaline presence, more prominently augmented IL-2 production and proliferation of CD4 + lymphocytes in male than female rat dLN cell cultures. In neuroantigen-stimulated dLN cells of both sexes propranolol increased IL-1 beta and IL-23/p19 expression and IL-17 + CD4 + cell frequency, but enhanced IL-17 production only in male rat CD4 + lymphocytes, thereby abrogating sexual dimorphism in IL-17 concentration observed in propranolol-free cultures. Thus, beta-adrenoceptor-mediated signalling may contribute to sex bias in rat IL-17-producing cell secretory capacity.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Cellular Immunology",
title = "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?",
pages = "57-48",
volume = "336",
doi = "10.1016/j.cellimm.2018.12.009"
}
Vujnović, I., Pilipović, I., Jasnić, N., Petrović, R., Blagojević, V., Arsenović-Ranin, N., Stojić-Vukanić, Z., Đorđević, J.,& Leposavić, G.. (2019). Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology
Academic Press Inc Elsevier Science, San Diego., 336, 48-57.
https://doi.org/10.1016/j.cellimm.2018.12.009
Vujnović I, Pilipović I, Jasnić N, Petrović R, Blagojević V, Arsenović-Ranin N, Stojić-Vukanić Z, Đorđević J, Leposavić G. Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?. in Cellular Immunology. 2019;336:48-57.
doi:10.1016/j.cellimm.2018.12.009 .
Vujnović, Ivana, Pilipović, Ivan, Jasnić, Nebojša, Petrović, Raisa, Blagojević, Veljko, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Đorđević, Jelena, Leposavić, Gordana, "Noradrenaline through beta-adrenoceptor contributes to sexual dimorphism in primary CD4+T-cell response in DA rat EAE model?" in Cellular Immunology, 336 (2019):48-57,
https://doi.org/10.1016/j.cellimm.2018.12.009 . .
1
14
9
13

Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor

Pilipović, Ivan; Vujnović, Ivana; Stojić-Vukanić, Zorica; Petrović, Raisa; Kosec, Duško; Nacka-Aleksić, Mirjana; Jasnić, Nebojša; Leposavić, Gordana

(Humana Press Inc, Totowa, 2019)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Stojić-Vukanić, Zorica
AU  - Petrović, Raisa
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Jasnić, Nebojša
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/531
AB  - Pharmacological blockade of alpha(1)-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined alpha(1)-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express alpha(1)-adrenoceptor. The analysis of influence of alpha(1)-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-beta expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1 beta and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through alpha(1)-adrenoceptor and consequently CD4+ T cell priming.
PB  - Humana Press Inc, Totowa
T2  - Immunologic Research
T1  - Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor
EP  - 240
IS  - 2-3
SP  - 223
VL  - 67
DO  - 10.1007/s12026-019-09082-y
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Stojić-Vukanić, Zorica and Petrović, Raisa and Kosec, Duško and Nacka-Aleksić, Mirjana and Jasnić, Nebojša and Leposavić, Gordana",
year = "2019",
abstract = "Pharmacological blockade of alpha(1)-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined alpha(1)-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express alpha(1)-adrenoceptor. The analysis of influence of alpha(1)-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-beta expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1 beta and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through alpha(1)-adrenoceptor and consequently CD4+ T cell priming.",
publisher = "Humana Press Inc, Totowa",
journal = "Immunologic Research",
title = "Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor",
pages = "240-223",
number = "2-3",
volume = "67",
doi = "10.1007/s12026-019-09082-y"
}
Pilipović, I., Vujnović, I., Stojić-Vukanić, Z., Petrović, R., Kosec, D., Nacka-Aleksić, M., Jasnić, N.,& Leposavić, G.. (2019). Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor. in Immunologic Research
Humana Press Inc, Totowa., 67(2-3), 223-240.
https://doi.org/10.1007/s12026-019-09082-y
Pilipović I, Vujnović I, Stojić-Vukanić Z, Petrović R, Kosec D, Nacka-Aleksić M, Jasnić N, Leposavić G. Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor. in Immunologic Research. 2019;67(2-3):223-240.
doi:10.1007/s12026-019-09082-y .
Pilipović, Ivan, Vujnović, Ivana, Stojić-Vukanić, Zorica, Petrović, Raisa, Kosec, Duško, Nacka-Aleksić, Mirjana, Jasnić, Nebojša, Leposavić, Gordana, "Noradrenaline modulates CD4+T cell priming in rat experimental autoimmune encephalomyelitis: a role for the alpha(1)-adrenoceptor" in Immunologic Research, 67, no. 2-3 (2019):223-240,
https://doi.org/10.1007/s12026-019-09082-y . .
1
13
6
13

Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine

Petrović, Raisa; Arsenović-Ranin, Nevena; Bufan, Biljana; Živković, Irena; Prijić, Ivana; Stoiljković, Vera; Leposavić, Gordana

(Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia, 2019)

TY  - CONF
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Bufan, Biljana
AU  - Živković, Irena
AU  - Prijić, Ivana
AU  - Stoiljković, Vera
AU  - Leposavić, Gordana
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/692
AB  - Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.
PB  - Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia
C3  - Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
T1  - Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine
UR  - https://hdl.handle.net/21.15107/rcub_intor_692
ER  - 
@conference{
author = "Petrović, Raisa and Arsenović-Ranin, Nevena and Bufan, Biljana and Živković, Irena and Prijić, Ivana and Stoiljković, Vera and Leposavić, Gordana",
year = "2019",
abstract = "Efficacy of the immune response to vaccine depends on genetic background, sex and
age of the recipient. However, mechanisms underlying this phenomenon have not been
elucidated, yet. The study investigated influence of sex and age on serum IgG response
to seasonal trivalent inactivated split influenza vaccine (TIV) in BALB/c and C57BL/6
mice, and mechanisms underlying this response. Total serum IgG responses to
influenza virus type A strains declined with aging, in a strain-specific manner.
Consequently, strain differences (greater IgG responses in BALB/c mice) observed in
young mice (three-month-old) were abrogated in old (eighteen-month-old) ones.
However, irrespective of strain and age, females developed stronger influenza type Aspecific IgG responses than males. Despite age-related decrease in influenza B-specific
serum IgG response, it was comparable between old BALB/c and C57BL/6 mice. The
strain/sex-specific differences in age-related changes in the magnitudes of IgG
responses to TIV correlated with those in number of germinal centre (GC) B
splenocytes. These differences were related to those in B splenocyte and CD4+
splenocyte proliferation in culture upon restimulation with influenza viruses from TIV.
The magnitudes of IgG responses also correlated to T follicular regulatory (Tfr)/T
follicular helper and Tfr/GC B splenocyte ratios across all groups of mice. Aging,
irrespective of influenza virus-specificity, affected serum IgG2a(c)/IgG1 ratios
(reflecting IFN-γ/IL-4 production level ratio) in male BALB/c and female C57BL/6
mice, respectively. Thus, although in young mice of both strains these ratios were
comparable between sexes, in old females they were shifted towards IgG1 when
compared with age-matched males. Consistently, the IFN-γ/IL-4 production level ratios
in splenocyte cultures stimulated with influenza viruses from old females of both strains
were shifted towards IL-4 compared with that in age-matched male cultures. The study
stimulates further research to formulate sex-specific strategies to improve efficacy of
influenza vaccine in elderly.",
publisher = "Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia",
journal = "Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th",
title = "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine",
url = "https://hdl.handle.net/21.15107/rcub_intor_692"
}
Petrović, R., Arsenović-Ranin, N., Bufan, B., Živković, I., Prijić, I., Stoiljković, V.,& Leposavić, G.. (2019). Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th
Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade Immunological Society of Serbia..
https://hdl.handle.net/21.15107/rcub_intor_692
Petrović R, Arsenović-Ranin N, Bufan B, Živković I, Prijić I, Stoiljković V, Leposavić G. Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine. in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th. 2019;.
https://hdl.handle.net/21.15107/rcub_intor_692 .
Petrović, Raisa, Arsenović-Ranin, Nevena, Bufan, Biljana, Živković, Irena, Prijić, Ivana, Stoiljković, Vera, Leposavić, Gordana, "Influence of ageing on sex and strain differences in immune response to inactivated influenza vaccine" in Immunology at the confluence of multidisciplinary approaches: Abstract book, Hotel Mona Plaza, Belgrade, December 6th-8th (2019),
https://hdl.handle.net/21.15107/rcub_intor_692 .

Potential impact of early-life probiotic supplementation on peritoneal macrophage function

Blagojević, Veljko; Petrović, Raisa; Ćuruvija, Ivana; Prijić, Ivana; Vujić, Vesna; Stanojević, Stanislava

(Belgrade: Institute for Biological Research "Siniša Stanković", 2019)

TY  - CONF
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Ćuruvija, Ivana
AU  - Prijić, Ivana
AU  - Vujić, Vesna
AU  - Stanojević, Stanislava
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/665
AB  - Clinical and animal trials show that early life probiotic consumption provides health benefits in adult life by modulating the immune response. We tested the effects of early life oral consumption of the probiotic Lactobacillus rhamnosus on the function and phenotype of rat peritoneal cavity cells in a model of induced colitis. For the first month of their lives, rats were either fed with an aqueous probiotic bacteria suspension (LB group) or tap water (control group). When the rats grew to 3 months old, we studied the response of their peritoneal macrophages to autologous fecal bacteria stimulation in vitro, both before and after colitis induction (TNBS 40mg/kg of body mass in 50% ethanol). Compared to the controls, the peritoneal cavity cells of the LB group produced less nitric oxide (NO) and had an increased proportion of CD163+ cells. The rats in the LB group have shown milder symptoms of colitis (shorter length of colon under necrosis, less severe submucosal infiltration, lesser degree of colonic wall thickening), along with a diminished increase of peritoneal proinflammatory CCR7+ cells and blunted NO production in response to stimulation by autologous fecal bacteria. Our results may indicate that early oral probiotic administration attenuates macrophage responses to fecal bacteria, which are the primary cause of tissue inflammation and necrosis in chemically induced colitis models, and that this attenuation may be involved in improving the health of colitic rats.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"
PB  - University of Belgrade; Immunological Society of Serbia
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Potential impact of early-life probiotic supplementation on peritoneal macrophage function
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_intor_665
ER  - 
@conference{
author = "Blagojević, Veljko and Petrović, Raisa and Ćuruvija, Ivana and Prijić, Ivana and Vujić, Vesna and Stanojević, Stanislava",
year = "2019",
abstract = "Clinical and animal trials show that early life probiotic consumption provides health benefits in adult life by modulating the immune response. We tested the effects of early life oral consumption of the probiotic Lactobacillus rhamnosus on the function and phenotype of rat peritoneal cavity cells in a model of induced colitis. For the first month of their lives, rats were either fed with an aqueous probiotic bacteria suspension (LB group) or tap water (control group). When the rats grew to 3 months old, we studied the response of their peritoneal macrophages to autologous fecal bacteria stimulation in vitro, both before and after colitis induction (TNBS 40mg/kg of body mass in 50% ethanol). Compared to the controls, the peritoneal cavity cells of the LB group produced less nitric oxide (NO) and had an increased proportion of CD163+ cells. The rats in the LB group have shown milder symptoms of colitis (shorter length of colon under necrosis, less severe submucosal infiltration, lesser degree of colonic wall thickening), along with a diminished increase of peritoneal proinflammatory CCR7+ cells and blunted NO production in response to stimulation by autologous fecal bacteria. Our results may indicate that early oral probiotic administration attenuates macrophage responses to fecal bacteria, which are the primary cause of tissue inflammation and necrosis in chemically induced colitis models, and that this attenuation may be involved in improving the health of colitic rats.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Potential impact of early-life probiotic supplementation on peritoneal macrophage function",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_intor_665"
}
Blagojević, V., Petrović, R., Ćuruvija, I., Prijić, I., Vujić, V.,& Stanojević, S.. (2019). Potential impact of early-life probiotic supplementation on peritoneal macrophage function. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"., 34.
https://hdl.handle.net/21.15107/rcub_intor_665
Blagojević V, Petrović R, Ćuruvija I, Prijić I, Vujić V, Stanojević S. Potential impact of early-life probiotic supplementation on peritoneal macrophage function. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:34.
https://hdl.handle.net/21.15107/rcub_intor_665 .
Blagojević, Veljko, Petrović, Raisa, Ćuruvija, Ivana, Prijić, Ivana, Vujić, Vesna, Stanojević, Stanislava, "Potential impact of early-life probiotic supplementation on peritoneal macrophage function" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):34,
https://hdl.handle.net/21.15107/rcub_intor_665 .

17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner

Ćuruvija, Ivana; Stanojević, Stanislava; Blagojević, Veljko; Petrović, Raisa; Prijić, Ivana; Vujić, Vesna

(Belgrade: Institute for Biological Research "Siniša Stanković", 2019)

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Prijić, Ivana
AU  - Vujić, Vesna
PY  - 2019
UR  - http://intor.torlakinstitut.com/handle/123456789/664
AB  - Aging differently affects the expression of estrogen receptors alpha and beta
(ERα and ERβ) and Toll-like receptors (TLR4) on peritoneal cavity cells of
male and female rats. We explored the involvement of ERα and ERβ in the in
vitro treatment of LPS-stimulated peritoneal macrophages with 17β-estradiol
(which stimulates both receptors) or genistein (which is predominantly an ERβ
agonist) on inflammatory cytokine secretion from young (3 months old) and
middle-aged (16 months old) female and male AO rats. Aging diminished the
proportion of TLR4+ cells and secretion of IL-1β and IL-6 in macrophages
from female rats while the effect on male rat macrophages was opposite. 17βestradiol increased IL-1β secretion by middle-aged females’ macrophages via
ERα, and suppressed it in cells from young females via ERβ. Genistein-induced
decrease of IL-1β in macrophages from all experimental groups was probably
mediated by ERβ. 17β-estradiol augmented IL-6 secretion by cells from all
experimental groups via ERα while genistein diminished it in all females’ and
in middle-aged male rats’ macrophages by activating ERβ. However, genistein
increased IL-6 secretion from macrophages of young male rats via ERα.
Although 17β-estradiol and genistein stimulated secretion of macrophage
inflammatory cytokines via ERα and suppressed it probably via ERβ, their
modulatory actions were determined by aging-induced changes in macrophage
ERs expression and possible ERα / ERβ interactions (Supported by Ministry of
Education, Science and Technological development, Republic of Serbia, Grant
No 175050).
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"
PB  - University of Belgrade; Immunological Society of Serbia
C3  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.
T1  - 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner
EP  - 132
SP  - 132
UR  - https://hdl.handle.net/21.15107/rcub_intor_664
ER  - 
@conference{
author = "Ćuruvija, Ivana and Stanojević, Stanislava and Blagojević, Veljko and Petrović, Raisa and Prijić, Ivana and Vujić, Vesna",
year = "2019",
abstract = "Aging differently affects the expression of estrogen receptors alpha and beta
(ERα and ERβ) and Toll-like receptors (TLR4) on peritoneal cavity cells of
male and female rats. We explored the involvement of ERα and ERβ in the in
vitro treatment of LPS-stimulated peritoneal macrophages with 17β-estradiol
(which stimulates both receptors) or genistein (which is predominantly an ERβ
agonist) on inflammatory cytokine secretion from young (3 months old) and
middle-aged (16 months old) female and male AO rats. Aging diminished the
proportion of TLR4+ cells and secretion of IL-1β and IL-6 in macrophages
from female rats while the effect on male rat macrophages was opposite. 17βestradiol increased IL-1β secretion by middle-aged females’ macrophages via
ERα, and suppressed it in cells from young females via ERβ. Genistein-induced
decrease of IL-1β in macrophages from all experimental groups was probably
mediated by ERβ. 17β-estradiol augmented IL-6 secretion by cells from all
experimental groups via ERα while genistein diminished it in all females’ and
in middle-aged male rats’ macrophages by activating ERβ. However, genistein
increased IL-6 secretion from macrophages of young male rats via ERα.
Although 17β-estradiol and genistein stimulated secretion of macrophage
inflammatory cytokines via ERα and suppressed it probably via ERβ, their
modulatory actions were determined by aging-induced changes in macrophage
ERs expression and possible ERα / ERβ interactions (Supported by Ministry of
Education, Science and Technological development, Republic of Serbia, Grant
No 175050).",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia",
journal = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.",
title = "17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner",
pages = "132-132",
url = "https://hdl.handle.net/21.15107/rcub_intor_664"
}
Ćuruvija, I., Stanojević, S., Blagojević, V., Petrović, R., Prijić, I.,& Vujić, V.. (2019). 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.
Belgrade: Institute for Biological Research "Siniša Stanković"., 132-132.
https://hdl.handle.net/21.15107/rcub_intor_664
Ćuruvija I, Stanojević S, Blagojević V, Petrović R, Prijić I, Vujić V. 17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner. in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia.. 2019;:132-132.
https://hdl.handle.net/21.15107/rcub_intor_664 .
Ćuruvija, Ivana, Stanojević, Stanislava, Blagojević, Veljko, Petrović, Raisa, Prijić, Ivana, Vujić, Vesna, "17β-Estradiol and genistein affect macrophage inflammatory cytokine production during aging in sex-specific manner" in Immunology at the Confluence of Multidisciplinary Approaches : abstract book: 2019 Dec 6-8; Belgrade, Serbia. (2019):132-132,
https://hdl.handle.net/21.15107/rcub_intor_664 .

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

Stojić-Vukanić, Zorica; Kotur-Stevuljević, Jelena; Nacka-Aleksić, Mirjana; Kosec, Duško; Vujnović, Ivana; Pilipović, Ivan; Dimitrijević, Mirjana; Leposavić, Gordana

(Springer, New York, 2018)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Kotur-Stevuljević, Jelena
AU  - Nacka-Aleksić, Mirjana
AU  - Kosec, Duško
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/518
AB  - In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.
PB  - Springer, New York
T2  - Molecular Neurobiology
T1  - Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action
EP  - 3774
IS  - 5
SP  - 3755
VL  - 55
DO  - 10.1007/s12035-017-0595-2
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Kotur-Stevuljević, Jelena and Nacka-Aleksić, Mirjana and Kosec, Duško and Vujnović, Ivana and Pilipović, Ivan and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2018",
abstract = "In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.",
publisher = "Springer, New York",
journal = "Molecular Neurobiology",
title = "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action",
pages = "3774-3755",
number = "5",
volume = "55",
doi = "10.1007/s12035-017-0595-2"
}
Stojić-Vukanić, Z., Kotur-Stevuljević, J., Nacka-Aleksić, M., Kosec, D., Vujnović, I., Pilipović, I., Dimitrijević, M.,& Leposavić, G.. (2018). Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology
Springer, New York., 55(5), 3755-3774.
https://doi.org/10.1007/s12035-017-0595-2
Stojić-Vukanić Z, Kotur-Stevuljević J, Nacka-Aleksić M, Kosec D, Vujnović I, Pilipović I, Dimitrijević M, Leposavić G. Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action. in Molecular Neurobiology. 2018;55(5):3755-3774.
doi:10.1007/s12035-017-0595-2 .
Stojić-Vukanić, Zorica, Kotur-Stevuljević, Jelena, Nacka-Aleksić, Mirjana, Kosec, Duško, Vujnović, Ivana, Pilipović, Ivan, Dimitrijević, Mirjana, Leposavić, Gordana, "Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action" in Molecular Neurobiology, 55, no. 5 (2018):3755-3774,
https://doi.org/10.1007/s12035-017-0595-2 . .
13
9
12

Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis

Stojić-Vukanić, Zorica; Pilipović, Ivan; Đikić, Jasmina; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Bufan, Biljana; Arsenović-Ranin, Nevena; Kosec, Duško; Leposavić, Gordana

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Đikić, Jasmina
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/516
AB  - The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis
EP  - 53
SP  - 37
VL  - 101
DO  - 10.1016/j.exger.2017.11.002
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Đikić, Jasmina and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Bufan, Biljana and Arsenović-Ranin, Nevena and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis",
pages = "53-37",
volume = "101",
doi = "10.1016/j.exger.2017.11.002"
}
Stojić-Vukanić, Z., Pilipović, I., Đikić, J., Vujnović, I., Nacka-Aleksić, M., Bufan, B., Arsenović-Ranin, N., Kosec, D.,& Leposavić, G.. (2018). Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 101, 37-53.
https://doi.org/10.1016/j.exger.2017.11.002
Stojić-Vukanić Z, Pilipović I, Đikić J, Vujnović I, Nacka-Aleksić M, Bufan B, Arsenović-Ranin N, Kosec D, Leposavić G. Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology. 2018;101:37-53.
doi:10.1016/j.exger.2017.11.002 .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Đikić, Jasmina, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Bufan, Biljana, Arsenović-Ranin, Nevena, Kosec, Duško, Leposavić, Gordana, "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis" in Experimental Gerontology, 101 (2018):37-53,
https://doi.org/10.1016/j.exger.2017.11.002 . .
8
5
8

Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?

Blagojević, Veljko; Kovačević-Jovanović, Vesna; Ćuruvija, Ivana; Petrović, Raisa; Vujnović, Ivana; Vujić, Vesna; Stanojević, Stanislava

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Blagojević, Veljko
AU  - Kovačević-Jovanović, Vesna
AU  - Ćuruvija, Ivana
AU  - Petrović, Raisa
AU  - Vujnović, Ivana
AU  - Vujić, Vesna
AU  - Stanojević, Stanislava
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/512
AB  - Aims: Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting auto-immunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus. Main methods: Rats were intraperitoneally injected with their own E. coli or Enterococcus. Peritoneal cells isolated two days later were tested for nitric oxide (NO) and cytokine production, and for arginase and myeloperoxidase (MPO) activity. The phenotype of cells was determined using flow cytometry. Key findings: While the Enterococcus injection did not affect the composition of peritoneal cells in AO rats, the E. coli treatment increased the percentages of activated CD11b(int)HIS48(hi) neutrophils, and decreased the proportion of resident (CD11b(hi)HIS48(int/low), CD163+ CD86+) and anti-inflammatory CD68+ CD206+ macrophages. E. coli increased the production of NO and urea, but preserved their ratio in cells from AO rats. Conversely, both E. coli and Enterococcus diminished the proportion of resident and anti-inflammatory macrophages, increased the proportion of activated neutrophils, and induced inflammatory polarization of peritoneal cells in DA rats. However, injection of E. coli maintained the ratio of typical CD11b(int)HIS48(int) neutrophils in DA rats, which correlated with the sustained MPO activity. Significance: The rat strain differences in peritoneal cell response to own commensal microbiota may contribute to differential susceptibility to inflammatory/autoimmune diseases.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?
EP  - 157
SP  - 147
VL  - 197
DO  - 10.1016/j.lfs.2018.02.011
ER  - 
@article{
author = "Blagojević, Veljko and Kovačević-Jovanović, Vesna and Ćuruvija, Ivana and Petrović, Raisa and Vujnović, Ivana and Vujić, Vesna and Stanojević, Stanislava",
year = "2018",
abstract = "Aims: Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting auto-immunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus. Main methods: Rats were intraperitoneally injected with their own E. coli or Enterococcus. Peritoneal cells isolated two days later were tested for nitric oxide (NO) and cytokine production, and for arginase and myeloperoxidase (MPO) activity. The phenotype of cells was determined using flow cytometry. Key findings: While the Enterococcus injection did not affect the composition of peritoneal cells in AO rats, the E. coli treatment increased the percentages of activated CD11b(int)HIS48(hi) neutrophils, and decreased the proportion of resident (CD11b(hi)HIS48(int/low), CD163+ CD86+) and anti-inflammatory CD68+ CD206+ macrophages. E. coli increased the production of NO and urea, but preserved their ratio in cells from AO rats. Conversely, both E. coli and Enterococcus diminished the proportion of resident and anti-inflammatory macrophages, increased the proportion of activated neutrophils, and induced inflammatory polarization of peritoneal cells in DA rats. However, injection of E. coli maintained the ratio of typical CD11b(int)HIS48(int) neutrophils in DA rats, which correlated with the sustained MPO activity. Significance: The rat strain differences in peritoneal cell response to own commensal microbiota may contribute to differential susceptibility to inflammatory/autoimmune diseases.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?",
pages = "157-147",
volume = "197",
doi = "10.1016/j.lfs.2018.02.011"
}
Blagojević, V., Kovačević-Jovanović, V., Ćuruvija, I., Petrović, R., Vujnović, I., Vujić, V.,& Stanojević, S.. (2018). Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 197, 147-157.
https://doi.org/10.1016/j.lfs.2018.02.011
Blagojević V, Kovačević-Jovanović V, Ćuruvija I, Petrović R, Vujnović I, Vujić V, Stanojević S. Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?. in Life Sciences. 2018;197:147-157.
doi:10.1016/j.lfs.2018.02.011 .
Blagojević, Veljko, Kovačević-Jovanović, Vesna, Ćuruvija, Ivana, Petrović, Raisa, Vujnović, Ivana, Vujić, Vesna, Stanojević, Stanislava, "Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?" in Life Sciences, 197 (2018):147-157,
https://doi.org/10.1016/j.lfs.2018.02.011 . .
1
5
3
5

Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis

Stanojević, Stanislava; Blagojević, Veljko; Ćuruvija, Ivana; Veljović, Katarina; Soković-Bajić, Svetlana; Kotur-Stevuljević, Jelena; Bogdanović, Andrija; Petrović, Raisa; Vujnović, Ivana; Kovačević-Jovanović, Vesna

(Elsevier Science Bv, Amsterdam, 2018)

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Veljović, Katarina
AU  - Soković-Bajić, Svetlana
AU  - Kotur-Stevuljević, Jelena
AU  - Bogdanović, Andrija
AU  - Petrović, Raisa
AU  - Vujnović, Ivana
AU  - Kovačević-Jovanović, Vesna
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/505
AB  - The current study investigated a potential modulating effect of orally applied Lactobacillus rhamnosus 64 (LB64) during the early postnatal period (day of life: similar to 3-30), during young adult period (day of life: 31-70) or throughout experiment, on parameters of trinitrobenzenesulfonic acid (TNBS)-induced colitis in adult rats. Treatment with LB64 during early postnatal, but not during young adult period reduced clinical damage score, neutrophil and macrophage infiltration into colon, the level of cytokine and myeloperoxidase (MPO) activity, but had no influence on other parameters of oxidative damage. Early postnatal treatment with LB64 also increased the diversity of fecal Bifidobacteria and Eubacteria, and improved maturation of ileal villi in 30-days old rats. When LB64 is applied during a critical period early in life, it affects immune system functioning of adults, probably by interactions with the mucosal immune system of the gastrointestinal tract that provides immune system maturation and shapes the overall immune response.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Functional Foods
T1  - Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis
EP  - 105
SP  - 92
VL  - 48
DO  - 10.1016/j.jff.2018.07.014
ER  - 
@article{
author = "Stanojević, Stanislava and Blagojević, Veljko and Ćuruvija, Ivana and Veljović, Katarina and Soković-Bajić, Svetlana and Kotur-Stevuljević, Jelena and Bogdanović, Andrija and Petrović, Raisa and Vujnović, Ivana and Kovačević-Jovanović, Vesna",
year = "2018",
abstract = "The current study investigated a potential modulating effect of orally applied Lactobacillus rhamnosus 64 (LB64) during the early postnatal period (day of life: similar to 3-30), during young adult period (day of life: 31-70) or throughout experiment, on parameters of trinitrobenzenesulfonic acid (TNBS)-induced colitis in adult rats. Treatment with LB64 during early postnatal, but not during young adult period reduced clinical damage score, neutrophil and macrophage infiltration into colon, the level of cytokine and myeloperoxidase (MPO) activity, but had no influence on other parameters of oxidative damage. Early postnatal treatment with LB64 also increased the diversity of fecal Bifidobacteria and Eubacteria, and improved maturation of ileal villi in 30-days old rats. When LB64 is applied during a critical period early in life, it affects immune system functioning of adults, probably by interactions with the mucosal immune system of the gastrointestinal tract that provides immune system maturation and shapes the overall immune response.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Functional Foods",
title = "Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis",
pages = "105-92",
volume = "48",
doi = "10.1016/j.jff.2018.07.014"
}
Stanojević, S., Blagojević, V., Ćuruvija, I., Veljović, K., Soković-Bajić, S., Kotur-Stevuljević, J., Bogdanović, A., Petrović, R., Vujnović, I.,& Kovačević-Jovanović, V.. (2018). Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis. in Journal of Functional Foods
Elsevier Science Bv, Amsterdam., 48, 92-105.
https://doi.org/10.1016/j.jff.2018.07.014
Stanojević S, Blagojević V, Ćuruvija I, Veljović K, Soković-Bajić S, Kotur-Stevuljević J, Bogdanović A, Petrović R, Vujnović I, Kovačević-Jovanović V. Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis. in Journal of Functional Foods. 2018;48:92-105.
doi:10.1016/j.jff.2018.07.014 .
Stanojević, Stanislava, Blagojević, Veljko, Ćuruvija, Ivana, Veljović, Katarina, Soković-Bajić, Svetlana, Kotur-Stevuljević, Jelena, Bogdanović, Andrija, Petrović, Raisa, Vujnović, Ivana, Kovačević-Jovanović, Vesna, "Oral treatment with Lactobacillus rhamnosus 64 during the early postnatal period improves the health of adult rats with TNBS-induced colitis" in Journal of Functional Foods, 48 (2018):92-105,
https://doi.org/10.1016/j.jff.2018.07.014 . .
6
4
2
4

The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats

Stanojević, Stanislava; Ćuruvija, Ivana; Blagojević, Veljko; Petrović, Raisa; Prijić, Ivana; Vujić, Vesna

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Prijić, Ivana
AU  - Vujić, Vesna
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/511
AB  - The systemic and extra- gonadal levels of 17 beta-estradiol (E2) change during aging, and affect the expression of estrogen receptors (ERs) in the immune cells of both females and males. The age-related cessation of ovarian function in females, as well as the tissue-specific expression of enzyme aromatase (estrogen synthase which significantly rises with the advancing age) in both males and females, both determine the concentration of E2 to which immune cells may be exposed. The present study was set up to investigate the direct influence of E2 in vitro on the secretory profile of peritoneal macrophages from young and naturally menopausal female rats, and from young and middle-aged male rats. The involvement of receptor(s) responsible for mediating the effects of E2 in vitro was examined by use of antagonists specific for ERa or ER beta. Whereas in macrophages from young female rats E2 treatment diminished interleukin (IL)-1 beta secretion, it increased it in young males, and the middleaged females. The in vitro E2 treatment increased tumor necrosis factor (TNF)-alpha release by macrophages from young rats of both sexes, while it increased macrophage IL-6 release independently of both sex and age. At the same time, E2 decreased hydrogen peroxide (H2O2) production in macrophages from females, and increased it in male rats of both ages, whereas it diminished nitric oxide (NO) release in all experimental groups. Inspite of the sex-and age-specific effects of E2 on macrophage urea release, E2 did not affect the NO/urea ratio in macrophages from female rats, and diminished it in macrophages from both young and middle-aged male rats. Independently of the sex and age, E2 stimulated the release of inflammatory cytokines predominantly via macrophage ER alpha, and inhibited the IL-1 beta release in young females via ER beta. In contrast, E2 increased macrophage H2O2 and urea production by activating ER beta, but diminished their release via ER alpha. Our study may contribute to better understanding of the complex role(s) that E2 may play in innate immunity during aging, and that are dependent of sex.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats
EP  - 94
SP  - 86
VL  - 113
DO  - 10.1016/j.exger.2018.09.024
ER  - 
@article{
author = "Stanojević, Stanislava and Ćuruvija, Ivana and Blagojević, Veljko and Petrović, Raisa and Prijić, Ivana and Vujić, Vesna",
year = "2018",
abstract = "The systemic and extra- gonadal levels of 17 beta-estradiol (E2) change during aging, and affect the expression of estrogen receptors (ERs) in the immune cells of both females and males. The age-related cessation of ovarian function in females, as well as the tissue-specific expression of enzyme aromatase (estrogen synthase which significantly rises with the advancing age) in both males and females, both determine the concentration of E2 to which immune cells may be exposed. The present study was set up to investigate the direct influence of E2 in vitro on the secretory profile of peritoneal macrophages from young and naturally menopausal female rats, and from young and middle-aged male rats. The involvement of receptor(s) responsible for mediating the effects of E2 in vitro was examined by use of antagonists specific for ERa or ER beta. Whereas in macrophages from young female rats E2 treatment diminished interleukin (IL)-1 beta secretion, it increased it in young males, and the middleaged females. The in vitro E2 treatment increased tumor necrosis factor (TNF)-alpha release by macrophages from young rats of both sexes, while it increased macrophage IL-6 release independently of both sex and age. At the same time, E2 decreased hydrogen peroxide (H2O2) production in macrophages from females, and increased it in male rats of both ages, whereas it diminished nitric oxide (NO) release in all experimental groups. Inspite of the sex-and age-specific effects of E2 on macrophage urea release, E2 did not affect the NO/urea ratio in macrophages from female rats, and diminished it in macrophages from both young and middle-aged male rats. Independently of the sex and age, E2 stimulated the release of inflammatory cytokines predominantly via macrophage ER alpha, and inhibited the IL-1 beta release in young females via ER beta. In contrast, E2 increased macrophage H2O2 and urea production by activating ER beta, but diminished their release via ER alpha. Our study may contribute to better understanding of the complex role(s) that E2 may play in innate immunity during aging, and that are dependent of sex.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats",
pages = "94-86",
volume = "113",
doi = "10.1016/j.exger.2018.09.024"
}
Stanojević, S., Ćuruvija, I., Blagojević, V., Petrović, R., Prijić, I.,& Vujić, V.. (2018). The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 113, 86-94.
https://doi.org/10.1016/j.exger.2018.09.024
Stanojević S, Ćuruvija I, Blagojević V, Petrović R, Prijić I, Vujić V. The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats. in Experimental Gerontology. 2018;113:86-94.
doi:10.1016/j.exger.2018.09.024 .
Stanojević, Stanislava, Ćuruvija, Ivana, Blagojević, Veljko, Petrović, Raisa, Prijić, Ivana, Vujić, Vesna, "The involvement of estrogen receptors alpha and beta in the in vitro effects of 17 beta-estradiol on secretory profile of peritoneal macrophages from naturally menopausal female and middle-aged male rats" in Experimental Gerontology, 113 (2018):86-94,
https://doi.org/10.1016/j.exger.2018.09.024 . .
3
2
4

Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats

Nacka-Aleksić, Mirjana; Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Bufan, Biljana; Dimitrijević, Mirjana; Leposavić, Gordana

(Elsevier Ireland Ltd, Clare, 2017)

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Bufan, Biljana
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/490
AB  - To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+T lymphocytes, including highly pathogenic IL-17+IFN-gamma+ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+cells (reflecting downregulated expression of IL-1 beta, IL-6 and IL-23/p19). On the other hand, when the neurological deficit reached maximum/plateau, in AO rat spinal cord was found lower CD4+FoxP3+CD25+ cell frequency followed by higher frequency of IL-10-producing CD8+T cells, which most likely also belong to regulatory T lymphocytes. Thus, the altered relation between regulatory T cell and effector CD4+T cell subsets was linked with persistence of mild neuroinflammation in AO rat EAE model. (C) 2017 Elsevier B.V. All rights reserved.
PB  - Elsevier Ireland Ltd, Clare
T2  - Mechanisms of Ageing and Development
T1  - Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats
EP  - 163
SP  - 146
VL  - 164
DO  - 10.1016/j.mad.2017.03.001
ER  - 
@article{
author = "Nacka-Aleksić, Mirjana and Stojić-Vukanić, Zorica and Pilipović, Ivan and Vujnović, Ivana and Bufan, Biljana and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2017",
abstract = "To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+T lymphocytes, including highly pathogenic IL-17+IFN-gamma+ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+cells (reflecting downregulated expression of IL-1 beta, IL-6 and IL-23/p19). On the other hand, when the neurological deficit reached maximum/plateau, in AO rat spinal cord was found lower CD4+FoxP3+CD25+ cell frequency followed by higher frequency of IL-10-producing CD8+T cells, which most likely also belong to regulatory T lymphocytes. Thus, the altered relation between regulatory T cell and effector CD4+T cell subsets was linked with persistence of mild neuroinflammation in AO rat EAE model. (C) 2017 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Mechanisms of Ageing and Development",
title = "Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats",
pages = "163-146",
volume = "164",
doi = "10.1016/j.mad.2017.03.001"
}
Nacka-Aleksić, M., Stojić-Vukanić, Z., Pilipović, I., Vujnović, I., Bufan, B., Dimitrijević, M.,& Leposavić, G.. (2017). Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats. in Mechanisms of Ageing and Development
Elsevier Ireland Ltd, Clare., 164, 146-163.
https://doi.org/10.1016/j.mad.2017.03.001
Nacka-Aleksić M, Stojić-Vukanić Z, Pilipović I, Vujnović I, Bufan B, Dimitrijević M, Leposavić G. Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats. in Mechanisms of Ageing and Development. 2017;164:146-163.
doi:10.1016/j.mad.2017.03.001 .
Nacka-Aleksić, Mirjana, Stojić-Vukanić, Zorica, Pilipović, Ivan, Vujnović, Ivana, Bufan, Biljana, Dimitrijević, Mirjana, Leposavić, Gordana, "Strain specificities in cellular and molecular immunopathogenic mechanisms underlying development of experimental autoimmune encephalomyelitis in aged rats" in Mechanisms of Ageing and Development, 164 (2017):146-163,
https://doi.org/10.1016/j.mad.2017.03.001 . .
1
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7
9

Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit

Dimitrijević, Mirjana; Kotur-Stevuljević, Jelena; Stojić-Vukanić, Zorica; Vujnović, Ivana; Pilipović, Ivan; Nacka-Aleksić, Mirjana; Leposavić, Gordana

(Springer/Plenum Publishers, New York, 2017)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Kotur-Stevuljević, Jelena
AU  - Stojić-Vukanić, Zorica
AU  - Vujnović, Ivana
AU  - Pilipović, Ivan
AU  - Nacka-Aleksić, Mirjana
AU  - Leposavić, Gordana
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/489
AB  - The study examined (a) whether there is sex difference in spinal cord and plasma oxidative stress profiles in Dark Agouti rats immunised for experimental autoimmune encephalomyelitis (EAE), the principal experimental model of multiple sclerosis, and (b) whether there is correlation between the oxidative stress in spinal cord and neurological deficit. Regardless of rat sex, with the disease development xanthine oxidase (XO) activity and inducible nitric oxide synthase (iNOS) mRNA expression increased in spinal cord, whereas glutathione levels decreased. This was accompanied by the rise in spinal cord malondialdehyde level. On the other hand, with EAE development superoxide dismutase (SOD) activity decreased, while O-2 (-) concentration increased only in spinal cord of male rats. Consequently, SOD activity was lower, whereas O-2 (-) concentration was higher in spinal cord of male rats with clinically manifested EAE. XO activity and iNOS mRNA expression were also elevated in their spinal cord. Consistently, in the effector phase of EAE the concentration of advanced oxidation protein product (AOPP) was higher in spinal cord of male rats, which exhibit more severe neurological deficit than their female counterparts. In as much as data obtained in the experimental models could be translated to humans, the findings may be relevant for designing sex-specific antioxidant therapeutic strategies. Furthermore, the study indicated that the increased pro-oxidant-antioxidant balance in plasma may be an early indicator of EAE development. Moreover, it showed that plasma AOPP level may indicate not only actual activity of the disease, but also serve to predict severity of its course.
PB  - Springer/Plenum Publishers, New York
T2  - Neurochemical Research
T1  - Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit
EP  - 492
IS  - 2
SP  - 481
VL  - 42
DO  - 10.1007/s11064-016-2094-7
ER  - 
@article{
author = "Dimitrijević, Mirjana and Kotur-Stevuljević, Jelena and Stojić-Vukanić, Zorica and Vujnović, Ivana and Pilipović, Ivan and Nacka-Aleksić, Mirjana and Leposavić, Gordana",
year = "2017",
abstract = "The study examined (a) whether there is sex difference in spinal cord and plasma oxidative stress profiles in Dark Agouti rats immunised for experimental autoimmune encephalomyelitis (EAE), the principal experimental model of multiple sclerosis, and (b) whether there is correlation between the oxidative stress in spinal cord and neurological deficit. Regardless of rat sex, with the disease development xanthine oxidase (XO) activity and inducible nitric oxide synthase (iNOS) mRNA expression increased in spinal cord, whereas glutathione levels decreased. This was accompanied by the rise in spinal cord malondialdehyde level. On the other hand, with EAE development superoxide dismutase (SOD) activity decreased, while O-2 (-) concentration increased only in spinal cord of male rats. Consequently, SOD activity was lower, whereas O-2 (-) concentration was higher in spinal cord of male rats with clinically manifested EAE. XO activity and iNOS mRNA expression were also elevated in their spinal cord. Consistently, in the effector phase of EAE the concentration of advanced oxidation protein product (AOPP) was higher in spinal cord of male rats, which exhibit more severe neurological deficit than their female counterparts. In as much as data obtained in the experimental models could be translated to humans, the findings may be relevant for designing sex-specific antioxidant therapeutic strategies. Furthermore, the study indicated that the increased pro-oxidant-antioxidant balance in plasma may be an early indicator of EAE development. Moreover, it showed that plasma AOPP level may indicate not only actual activity of the disease, but also serve to predict severity of its course.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Neurochemical Research",
title = "Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit",
pages = "492-481",
number = "2",
volume = "42",
doi = "10.1007/s11064-016-2094-7"
}
Dimitrijević, M., Kotur-Stevuljević, J., Stojić-Vukanić, Z., Vujnović, I., Pilipović, I., Nacka-Aleksić, M.,& Leposavić, G.. (2017). Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit. in Neurochemical Research
Springer/Plenum Publishers, New York., 42(2), 481-492.
https://doi.org/10.1007/s11064-016-2094-7
Dimitrijević M, Kotur-Stevuljević J, Stojić-Vukanić Z, Vujnović I, Pilipović I, Nacka-Aleksić M, Leposavić G. Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit. in Neurochemical Research. 2017;42(2):481-492.
doi:10.1007/s11064-016-2094-7 .
Dimitrijević, Mirjana, Kotur-Stevuljević, Jelena, Stojić-Vukanić, Zorica, Vujnović, Ivana, Pilipović, Ivan, Nacka-Aleksić, Mirjana, Leposavić, Gordana, "Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit" in Neurochemical Research, 42, no. 2 (2017):481-492,
https://doi.org/10.1007/s11064-016-2094-7 . .
17
10
16

Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro

Petrović, Raisa; Dimitrijević, Mirjana; Stanojević, Stanislava; Blagojević, Veljko; Ćuruvija, Ivana; Vujnović, Ivana; Arsenović-Ranin, Nevena; Vujić, Vesna; Leposavić, Gordana

(2016)

TY  - CONF
AU  - Petrović, Raisa
AU  - Dimitrijević, Mirjana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Vujnović, Ivana
AU  - Arsenović-Ranin, Nevena
AU  - Vujić, Vesna
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/669
AB  - Cilj rada je bio da se ispita uticaj starenja na aktivnost makrofaga aktivisanih M1/M2 polarizujućim faktorima. Peritonealne rezidentne makrofage (rMf) i tioglikolatom-indukovane makrofage (trFm) mladih (3 meseca) i starih (18-19) meseci pacova su kultivisane u prisustvu stimulatora klasične (M1) – lipopolisaharida (LPS) i faktora stimulacije kolonija granulocita i makrofaga (GM-CSF), i alternativne (M2) aktivacije makrofaga – interleukina-4 (IL-4), ili u odsustvu poznatih simulatora. Ispitivana je sposobnost fagocitozr zimozana i sekrecije inflamatornih medijatora. Starenjem se povećavala učestalost makrofaga monocitnog porekla (CCR*7CD68* ćelije) u okviru populacije rMf, dok je u okviru populacije tgMf nađena povećana učestalost makrofaga najzrelijeg fenotipa (CD163*CD68* ćelije). Nijedan od ispitivanih stimulatora nije uticao na fagocitnu sposobnost rMf i tgMf. Povećana sekrecija IL-1β, IL-6 I IL-10 I smanjena sekrecija TGF-β u odgovoru na stimulaciju LPS-om je nađena kod rMf i tgMF pacova obe starosti. GM-CSF je povećao sekreciju  IL-1β i IL-6 kod rMf starih pacova i tgMf mladih pacova. Paradoksalno, IL-4 je povećao sekreciju pro-inflamatornih citokina,  IL-1β i IL-6, kod rMf starih pacova. Starenjem se metabolizam arginina i u rMf i u tgMf usmeravao ka sintezi uree. Rezultati su pokazali da sa starenjem tgMf gube sposobnost polatizacije pod uticajem GM-CSF, i da rMf pod uticajem IL-4 polarizuju prema pro-inflamatornom M1 sekretornom fenotipu. Gubitak kontrole sekrecije inflamatornih medijatora iz makrofaga u odgovoru na M1/M2 aktivatore mogao bi da doprinese povećanom riziku od oboljevanja od infektivnih i inflamatornih bolesti u starosti.
C3  - VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata
T1  - Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro
UR  - https://hdl.handle.net/21.15107/rcub_intor_669
ER  - 
@conference{
author = "Petrović, Raisa and Dimitrijević, Mirjana and Stanojević, Stanislava and Blagojević, Veljko and Ćuruvija, Ivana and Vujnović, Ivana and Arsenović-Ranin, Nevena and Vujić, Vesna and Leposavić, Gordana",
year = "2016",
abstract = "Cilj rada je bio da se ispita uticaj starenja na aktivnost makrofaga aktivisanih M1/M2 polarizujućim faktorima. Peritonealne rezidentne makrofage (rMf) i tioglikolatom-indukovane makrofage (trFm) mladih (3 meseca) i starih (18-19) meseci pacova su kultivisane u prisustvu stimulatora klasične (M1) – lipopolisaharida (LPS) i faktora stimulacije kolonija granulocita i makrofaga (GM-CSF), i alternativne (M2) aktivacije makrofaga – interleukina-4 (IL-4), ili u odsustvu poznatih simulatora. Ispitivana je sposobnost fagocitozr zimozana i sekrecije inflamatornih medijatora. Starenjem se povećavala učestalost makrofaga monocitnog porekla (CCR*7CD68* ćelije) u okviru populacije rMf, dok je u okviru populacije tgMf nađena povećana učestalost makrofaga najzrelijeg fenotipa (CD163*CD68* ćelije). Nijedan od ispitivanih stimulatora nije uticao na fagocitnu sposobnost rMf i tgMf. Povećana sekrecija IL-1β, IL-6 I IL-10 I smanjena sekrecija TGF-β u odgovoru na stimulaciju LPS-om je nađena kod rMf i tgMF pacova obe starosti. GM-CSF je povećao sekreciju  IL-1β i IL-6 kod rMf starih pacova i tgMf mladih pacova. Paradoksalno, IL-4 je povećao sekreciju pro-inflamatornih citokina,  IL-1β i IL-6, kod rMf starih pacova. Starenjem se metabolizam arginina i u rMf i u tgMf usmeravao ka sintezi uree. Rezultati su pokazali da sa starenjem tgMf gube sposobnost polatizacije pod uticajem GM-CSF, i da rMf pod uticajem IL-4 polarizuju prema pro-inflamatornom M1 sekretornom fenotipu. Gubitak kontrole sekrecije inflamatornih medijatora iz makrofaga u odgovoru na M1/M2 aktivatore mogao bi da doprinese povećanom riziku od oboljevanja od infektivnih i inflamatornih bolesti u starosti.",
journal = "VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata",
title = "Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro",
url = "https://hdl.handle.net/21.15107/rcub_intor_669"
}
Petrović, R., Dimitrijević, M., Stanojević, S., Blagojević, V., Ćuruvija, I., Vujnović, I., Arsenović-Ranin, N., Vujić, V.,& Leposavić, G.. (2016). Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro. in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata.
https://hdl.handle.net/21.15107/rcub_intor_669
Petrović R, Dimitrijević M, Stanojević S, Blagojević V, Ćuruvija I, Vujnović I, Arsenović-Ranin N, Vujić V, Leposavić G. Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro. in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata. 2016;.
https://hdl.handle.net/21.15107/rcub_intor_669 .
Petrović, Raisa, Dimitrijević, Mirjana, Stanojević, Stanislava, Blagojević, Veljko, Ćuruvija, Ivana, Vujnović, Ivana, Arsenović-Ranin, Nevena, Vujić, Vesna, Leposavić, Gordana, "Starenje utiče na M1/M2 polarizaciju rezidentnih peritonealnih makrofaga pacova stimulisanih in vitro" in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata (2016),
https://hdl.handle.net/21.15107/rcub_intor_669 .

Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4

Dimitrijević, Mirjana; Stanojević, Stanislava; Blagojević, Veljko; Ćuruvija, Ivana; Vujnović, Ivana; Petrović, Raisa; Arsenović-Ranin, Nevena; Vujić, Vesna; Leposavić, Gordana

(Springer, New York, 2016)

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Vujnović, Ivana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Vujić, Vesna
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/466
AB  - Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18-19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1 beta, IL-6 and IL-10 and downregulated that of TGF-beta was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1 beta and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1 beta and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.
PB  - Springer, New York
T2  - Biogerontology
T1  - Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4
EP  - 371
IS  - 2
SP  - 359
VL  - 17
DO  - 10.1007/s10522-015-9620-x
ER  - 
@article{
author = "Dimitrijević, Mirjana and Stanojević, Stanislava and Blagojević, Veljko and Ćuruvija, Ivana and Vujnović, Ivana and Petrović, Raisa and Arsenović-Ranin, Nevena and Vujić, Vesna and Leposavić, Gordana",
year = "2016",
abstract = "Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18-19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1 beta, IL-6 and IL-10 and downregulated that of TGF-beta was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1 beta and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1 beta and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4",
pages = "371-359",
number = "2",
volume = "17",
doi = "10.1007/s10522-015-9620-x"
}
Dimitrijević, M., Stanojević, S., Blagojević, V., Ćuruvija, I., Vujnović, I., Petrović, R., Arsenović-Ranin, N., Vujić, V.,& Leposavić, G.. (2016). Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology
Springer, New York., 17(2), 359-371.
https://doi.org/10.1007/s10522-015-9620-x
Dimitrijević M, Stanojević S, Blagojević V, Ćuruvija I, Vujnović I, Petrović R, Arsenović-Ranin N, Vujić V, Leposavić G. Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4. in Biogerontology. 2016;17(2):359-371.
doi:10.1007/s10522-015-9620-x .
Dimitrijević, Mirjana, Stanojević, Stanislava, Blagojević, Veljko, Ćuruvija, Ivana, Vujnović, Ivana, Petrović, Raisa, Arsenović-Ranin, Nevena, Vujić, Vesna, Leposavić, Gordana, "Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4" in Biogerontology, 17, no. 2 (2016):359-371,
https://doi.org/10.1007/s10522-015-9620-x . .
22
16
20

Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro

Stojić-Vukanić, Zorica; Bufan, Biljana; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Leposavić, Gordana

(Elsevier, Amsterdam, 2016)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Bufan, Biljana
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/460
AB  - There are little data on modulatory effects of estrogens on rat dendritic cell (DC) responses to inflammatory stimuli, and consequently their ability to activate and polarize CD4+ T lymphocyte-mediated immune responses. Splenic conventional DCs from young female Albino Oxford rats were activated in vitro with LPS (TLR4 agonist) or R848 (TLR7/8 agonist) in the presence and absence of 17 beta-estradiol (E2), and their allostimulatory and CD4+ lymphocyte polarizing ability in mixed leukocyte culture (MLC) were studied. Irrespective of the E2 presence, LPS and R848 up-regulated the expression of MHC II on DCs, so they exhibited enhanced allostimulatory capacity in co-culture with CD4+ lymphocytes. On the other hand, E2 promoted stimulatory action of both TLRs on OX62+ DC IL-23 production, augmented their stimulatory effects on IL-6 and IL-1 beta production, but diminished their enhancing effects on the expression IL-10 and IL-27 by DCs. Consequently, in MLC, OX62+ DCs activated/matured in the co-presence of E2 and either LPS or R848 increased the levels of IL-17, the signature Th17 cell cytoldne, when compared with those activated/matured in the absence of E2. GM-CSF levels were also increased in these MLC. Given that the expression of IL-7 mRNA was diminished in DCs activated/matured in the co presence of E2 and TLR, this increase most likely did not reflect enhanced differentiation of Th cells producing GM-CSF only (Th-GM). Conclusions: E2 augments capacity of LPS- and R848-activated/matured DCs from young rat spleen to induce differentiation of IL-17- and GM-CSF-producing cells. (C) 2016 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - International Immunopharmacology
T1  - Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro
EP  - 253
SP  - 244
VL  - 40
DO  - 10.1016/j.intimp.2016.09.001
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Bufan, Biljana and Pilipović, Ivan and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Petrović, Raisa and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2016",
abstract = "There are little data on modulatory effects of estrogens on rat dendritic cell (DC) responses to inflammatory stimuli, and consequently their ability to activate and polarize CD4+ T lymphocyte-mediated immune responses. Splenic conventional DCs from young female Albino Oxford rats were activated in vitro with LPS (TLR4 agonist) or R848 (TLR7/8 agonist) in the presence and absence of 17 beta-estradiol (E2), and their allostimulatory and CD4+ lymphocyte polarizing ability in mixed leukocyte culture (MLC) were studied. Irrespective of the E2 presence, LPS and R848 up-regulated the expression of MHC II on DCs, so they exhibited enhanced allostimulatory capacity in co-culture with CD4+ lymphocytes. On the other hand, E2 promoted stimulatory action of both TLRs on OX62+ DC IL-23 production, augmented their stimulatory effects on IL-6 and IL-1 beta production, but diminished their enhancing effects on the expression IL-10 and IL-27 by DCs. Consequently, in MLC, OX62+ DCs activated/matured in the co-presence of E2 and either LPS or R848 increased the levels of IL-17, the signature Th17 cell cytoldne, when compared with those activated/matured in the absence of E2. GM-CSF levels were also increased in these MLC. Given that the expression of IL-7 mRNA was diminished in DCs activated/matured in the co presence of E2 and TLR, this increase most likely did not reflect enhanced differentiation of Th cells producing GM-CSF only (Th-GM). Conclusions: E2 augments capacity of LPS- and R848-activated/matured DCs from young rat spleen to induce differentiation of IL-17- and GM-CSF-producing cells. (C) 2016 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "International Immunopharmacology",
title = "Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro",
pages = "253-244",
volume = "40",
doi = "10.1016/j.intimp.2016.09.001"
}
Stojić-Vukanić, Z., Bufan, B., Pilipović, I., Vujnović, I., Nacka-Aleksić, M., Petrović, R., Arsenović-Ranin, N.,& Leposavić, G.. (2016). Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro. in International Immunopharmacology
Elsevier, Amsterdam., 40, 244-253.
https://doi.org/10.1016/j.intimp.2016.09.001
Stojić-Vukanić Z, Bufan B, Pilipović I, Vujnović I, Nacka-Aleksić M, Petrović R, Arsenović-Ranin N, Leposavić G. Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro. in International Immunopharmacology. 2016;40:244-253.
doi:10.1016/j.intimp.2016.09.001 .
Stojić-Vukanić, Zorica, Bufan, Biljana, Pilipović, Ivan, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Petrović, Raisa, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+lymphocytes into IL-17/GM-CSF-producing cells in vitro" in International Immunopharmacology, 40 (2016):244-253,
https://doi.org/10.1016/j.intimp.2016.09.001 . .
3
1
3

GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis

Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

(Public Library Science, San Francisco, 2016)

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Petrović, Raisa
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/457
AB  - Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis
IS  - 11
VL  - 11
DO  - 10.1371/journal.pone.0166498
ER  - 
@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Petrović, Raisa and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2016",
abstract = "Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+ IFN-gamma+, IL-17+ IFN-gamma-, and IL-17-IFN-gamma+ cells accompanied by higher frequency of IL-17-IFN-gamma- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+ IFN-gamma+ Th17 cells in SC) on GM-CSF+ IFN-gamma+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+ IFN-gamma+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1 beta, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45(hi) cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto) reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis",
number = "11",
volume = "11",
doi = "10.1371/journal.pone.0166498"
}
Stojić-Vukanić, Z., Pilipović, I., Vujnović, I., Nacka-Aleksić, M., Petrović, R., Arsenović-Ranin, N., Dimitrijević, M.,& Leposavić, G.. (2016). GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis. in PLoS One
Public Library Science, San Francisco., 11(11).
https://doi.org/10.1371/journal.pone.0166498
Stojić-Vukanić Z, Pilipović I, Vujnović I, Nacka-Aleksić M, Petrović R, Arsenović-Ranin N, Dimitrijević M, Leposavić G. GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis. in PLoS One. 2016;11(11).
doi:10.1371/journal.pone.0166498 .
Stojić-Vukanić, Zorica, Pilipović, Ivan, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Petrović, Raisa, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Leposavić, Gordana, "GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis" in PLoS One, 11, no. 11 (2016),
https://doi.org/10.1371/journal.pone.0166498 . .
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Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats

Pilipović, Ivan; Vujnović, Ivana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Kosec, Duško; Stojić-Vukanić, Zorica; Leposavić, Gordana

(Elsevier Science Bv, Amsterdam, 2016)

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vujnović, Ivana
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Kosec, Duško
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/454
AB  - The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and beta(2)- and alpha(1)-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average beta(2)- and alpha(1)-AR thymocyte surface density changed in the opposite direction with age; the density of beta(2)-AR decreased, whereas that of alpha(1)-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of beta(2)-ARs, but it increased that of alpha(1)-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age-and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats. (C) 2016 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats
EP  - 116
SP  - 103
VL  - 297
DO  - 10.1016/j.jneuroim.2016.05.017
ER  - 
@article{
author = "Pilipović, Ivan and Vujnović, Ivana and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Kosec, Duško and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2016",
abstract = "The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and beta(2)- and alpha(1)-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average beta(2)- and alpha(1)-AR thymocyte surface density changed in the opposite direction with age; the density of beta(2)-AR decreased, whereas that of alpha(1)-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of beta(2)-ARs, but it increased that of alpha(1)-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age-and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats. (C) 2016 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats",
pages = "116-103",
volume = "297",
doi = "10.1016/j.jneuroim.2016.05.017"
}
Pilipović, I., Vujnović, I., Arsenović-Ranin, N., Dimitrijević, M., Kosec, D., Stojić-Vukanić, Z.,& Leposavić, G.. (2016). Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. in Journal of Neuroimmunology
Elsevier Science Bv, Amsterdam., 297, 103-116.
https://doi.org/10.1016/j.jneuroim.2016.05.017
Pilipović I, Vujnović I, Arsenović-Ranin N, Dimitrijević M, Kosec D, Stojić-Vukanić Z, Leposavić G. Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats. in Journal of Neuroimmunology. 2016;297:103-116.
doi:10.1016/j.jneuroim.2016.05.017 .
Pilipović, Ivan, Vujnović, Ivana, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Kosec, Duško, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats" in Journal of Neuroimmunology, 297 (2016):103-116,
https://doi.org/10.1016/j.jneuroim.2016.05.017 . .
6
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Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner

Stanojević, Stanislava; Ćuruvija, Ivana; Blagojević, Veljko; Vujnović, Ivana; Petrović, Raisa; Dimitrijević, Mirjana; Leposavić, Gordana

(Immunological society of Serbia, 2015)

TY  - CONF
AU  - Stanojević, Stanislava
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Vujnović, Ivana
AU  - Petrović, Raisa
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/666
AB  - The present study was designed to examine influence of aging on
macrophage proinflammatory/anti-inflammatory capacity in rat model of
thioglycollate-induced peritonitis. Peritoneal macrophages were isolated
from young (3-months-old) and aged (18-months-old) Dark Agouti (DA)
and Albino Oxford (AO) rats seven days post-injection of thioglycollate
medium. Freshly isolated peritoneal exudate cells were examined for the
expression of CD163, CCR7, CD14 and TLR4, whereas cytokine
production (TNF-α, IL-6 and IL-10) and arginine metabolism end-products
(NO and urea) were assayed in vitro under basal conditions and following
stimulation with LPS. In DA rat inflammatory peritoneal exudate, aging
diminished the frequency of cells with a “resolving macrophage”
CD14+CD163+ phenotype. However, in AO rats, which exhibited stable
frequency of CD14+CD163+ cells in inflammatory peritoneal exudate with
aging, the proportion of CCR7-bearing peritoneal cells, presumably
immigrating inflammatory monocytes, was diminished in aged animals.
Under basal culture conditions, macrophages from aged rats of both strains
released less amount of TNF-α, IL-6 and IL-10, but produced more urea
than cells from young strain-matched rats. However, these changes were
more pronounced in peritoneal macrophages from AO rats. Additionally,
age-related decrease in the frequency of TLR4-expressing cells was
observed among fresh peritoneal exudate cells from AO rats. Upon LPS
stimulation, the production of prototypic inflammatory cytokines (TNF-α
and IL-6) was diminished in macrophages from aged AO rats, whereas
aging had the opposite effect on their production in DA rat macrophages.
Moreover, aging increased NO production in LPS-stimulated macrophages
from DA rats, whereas urea production was enhanced in macrophages from
both strains, but this increase was strikingly more pronounced in
macrophages from AO rats. Collectively, results suggest that aging affects
inflammatory peritoneal exudate cellular composition and macrophage
proinflamatory/immunomodulatory capacity in a strain- specific manner
PB  - Immunological society of Serbia
PB  - University of Kragujevac, Faculty of medical sciences
C3  - 3rd Belgrade EFIS symposium on immunoregulation. Book of abstracts: Immunity, Infection, Autoimmunity and Aging. Hotel Izvor, Arandjelovac Spa (Belgrade) 24-27 May 2015
T1  - Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner
EP  - 58
SP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_intor_666
ER  - 
@conference{
author = "Stanojević, Stanislava and Ćuruvija, Ivana and Blagojević, Veljko and Vujnović, Ivana and Petrović, Raisa and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2015",
abstract = "The present study was designed to examine influence of aging on
macrophage proinflammatory/anti-inflammatory capacity in rat model of
thioglycollate-induced peritonitis. Peritoneal macrophages were isolated
from young (3-months-old) and aged (18-months-old) Dark Agouti (DA)
and Albino Oxford (AO) rats seven days post-injection of thioglycollate
medium. Freshly isolated peritoneal exudate cells were examined for the
expression of CD163, CCR7, CD14 and TLR4, whereas cytokine
production (TNF-α, IL-6 and IL-10) and arginine metabolism end-products
(NO and urea) were assayed in vitro under basal conditions and following
stimulation with LPS. In DA rat inflammatory peritoneal exudate, aging
diminished the frequency of cells with a “resolving macrophage”
CD14+CD163+ phenotype. However, in AO rats, which exhibited stable
frequency of CD14+CD163+ cells in inflammatory peritoneal exudate with
aging, the proportion of CCR7-bearing peritoneal cells, presumably
immigrating inflammatory monocytes, was diminished in aged animals.
Under basal culture conditions, macrophages from aged rats of both strains
released less amount of TNF-α, IL-6 and IL-10, but produced more urea
than cells from young strain-matched rats. However, these changes were
more pronounced in peritoneal macrophages from AO rats. Additionally,
age-related decrease in the frequency of TLR4-expressing cells was
observed among fresh peritoneal exudate cells from AO rats. Upon LPS
stimulation, the production of prototypic inflammatory cytokines (TNF-α
and IL-6) was diminished in macrophages from aged AO rats, whereas
aging had the opposite effect on their production in DA rat macrophages.
Moreover, aging increased NO production in LPS-stimulated macrophages
from DA rats, whereas urea production was enhanced in macrophages from
both strains, but this increase was strikingly more pronounced in
macrophages from AO rats. Collectively, results suggest that aging affects
inflammatory peritoneal exudate cellular composition and macrophage
proinflamatory/immunomodulatory capacity in a strain- specific manner",
publisher = "Immunological society of Serbia, University of Kragujevac, Faculty of medical sciences",
journal = "3rd Belgrade EFIS symposium on immunoregulation. Book of abstracts: Immunity, Infection, Autoimmunity and Aging. Hotel Izvor, Arandjelovac Spa (Belgrade) 24-27 May 2015",
title = "Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner",
pages = "58-58",
url = "https://hdl.handle.net/21.15107/rcub_intor_666"
}
Stanojević, S., Ćuruvija, I., Blagojević, V., Vujnović, I., Petrović, R., Dimitrijević, M.,& Leposavić, G.. (2015). Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner. in 3rd Belgrade EFIS symposium on immunoregulation. Book of abstracts: Immunity, Infection, Autoimmunity and Aging. Hotel Izvor, Arandjelovac Spa (Belgrade) 24-27 May 2015
Immunological society of Serbia., 58-58.
https://hdl.handle.net/21.15107/rcub_intor_666
Stanojević S, Ćuruvija I, Blagojević V, Vujnović I, Petrović R, Dimitrijević M, Leposavić G. Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner. in 3rd Belgrade EFIS symposium on immunoregulation. Book of abstracts: Immunity, Infection, Autoimmunity and Aging. Hotel Izvor, Arandjelovac Spa (Belgrade) 24-27 May 2015. 2015;:58-58.
https://hdl.handle.net/21.15107/rcub_intor_666 .
Stanojević, Stanislava, Ćuruvija, Ivana, Blagojević, Veljko, Vujnović, Ivana, Petrović, Raisa, Dimitrijević, Mirjana, Leposavić, Gordana, "Aging affects rat inflammatory peritoneal exudate composition and macrophage inflammatory mediator production in a strain-dependent manner" in 3rd Belgrade EFIS symposium on immunoregulation. Book of abstracts: Immunity, Infection, Autoimmunity and Aging. Hotel Izvor, Arandjelovac Spa (Belgrade) 24-27 May 2015 (2015):58-58,
https://hdl.handle.net/21.15107/rcub_intor_666 .