TY  - CONF
AU  - Panić, Marko
AU  - Prijić, Ivana
AU  - Simić, Mihajlo
AU  - Ćuruvija, Ivana
AU  - Lukić, Ivana
AU  - Drgačević, Luka
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/880
AB  - Diphtheria and tetanus, once formidable causes of morbidity and mortality worldwide, have seen their threats markedly diminished through the advent and widespread use of vaccines. This review article delves into the historical journey of diphtheria and tetanus vaccines, evaluates their current status in global immunization programs, and explores future perspectives in their evolution and implementation. The inception of diphtheria and tetanus vaccines marked a pivotal shift in infectious disease control. The development of diphtheria toxoid by Emil von Behring in the late 19th century and the subsequent creation of tetanus toxoid in the early 20th century set the stage for large-scale immunization efforts. These efforts were bolstered in the mid-20th century with the integration of these toxoids into combination vaccines, notably the DTP (diphtheria-tetanus-pertussis) vaccine, facilitating broader immunization coverage and enhanced public health outcomes. Currently, the inclusion of diphtheria and tetanus vaccines in national immunization schedules has led to a significant decline in the incidence of these diseases globally. However, challenges remain, including disparities in vaccine coverage and the emergence of non-toxigenic strains causing diphtheria. The review highlights the WHO’s strategies towards achieving higher immunization coverage and the importance of maintaining high vaccination rates to prevent resurgence. Looking forward, the review discusses the ongoing research and development aimed at improving vaccine formulations, reducing adverse reactions, and enhancing the efficacy and durability of protection. Innovations such as nanoparticle vaccines and DNA vaccines are explored as potential avenues for future advancements. Additionally, the review addresses the critical role of global health governance in addressing vaccine hesitancy, improving access in low-resource settings, and coordinating responses to outbreaks. In conclusion, while the battle against diphtheria and tetanus has seen significant victories, continuous efforts in vaccine innovation, policy implementation, and global cooperation are essential to sustain these gains and achieve the ultimate goal of global eradication.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions
EP  - 169
SP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_intor_880
ER  - 

@conference{
author = "Panić, Marko and Prijić, Ivana and Simić, Mihajlo and Ćuruvija, Ivana and Lukić, Ivana and Drgačević, Luka and Kojić, Milan",
year = "2024",
abstract = "Diphtheria and tetanus, once formidable causes of morbidity and mortality worldwide, have seen their threats markedly diminished through the advent and widespread use of vaccines. This review article delves into the historical journey of diphtheria and tetanus vaccines, evaluates their current status in global immunization programs, and explores future perspectives in their evolution and implementation. The inception of diphtheria and tetanus vaccines marked a pivotal shift in infectious disease control. The development of diphtheria toxoid by Emil von Behring in the late 19th century and the subsequent creation of tetanus toxoid in the early 20th century set the stage for large-scale immunization efforts. These efforts were bolstered in the mid-20th century with the integration of these toxoids into combination vaccines, notably the DTP (diphtheria-tetanus-pertussis) vaccine, facilitating broader immunization coverage and enhanced public health outcomes. Currently, the inclusion of diphtheria and tetanus vaccines in national immunization schedules has led to a significant decline in the incidence of these diseases globally. However, challenges remain, including disparities in vaccine coverage and the emergence of non-toxigenic strains causing diphtheria. The review highlights the WHO’s strategies towards achieving higher immunization coverage and the importance of maintaining high vaccination rates to prevent resurgence. Looking forward, the review discusses the ongoing research and development aimed at improving vaccine formulations, reducing adverse reactions, and enhancing the efficacy and durability of protection. Innovations such as nanoparticle vaccines and DNA vaccines are explored as potential avenues for future advancements. Additionally, the review addresses the critical role of global health governance in addressing vaccine hesitancy, improving access in low-resource settings, and coordinating responses to outbreaks. In conclusion, while the battle against diphtheria and tetanus has seen significant victories, continuous efforts in vaccine innovation, policy implementation, and global cooperation are essential to sustain these gains and achieve the ultimate goal of global eradication.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions",
pages = "169-169",
url = "https://hdl.handle.net/21.15107/rcub_intor_880"
}

Panić, M., Prijić, I., Simić, M., Ćuruvija, I., Lukić, I., Drgačević, L.,& Kojić, M.. (2024). Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 169-169.
https://hdl.handle.net/21.15107/rcub_intor_880

Panić M, Prijić I, Simić M, Ćuruvija I, Lukić I, Drgačević L, Kojić M. Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:169-169.
https://hdl.handle.net/21.15107/rcub_intor_880 .

Panić, Marko, Prijić, Ivana, Simić, Mihajlo, Ćuruvija, Ivana, Lukić, Ivana, Drgačević, Luka, Kojić, Milan, "Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):169-169,
https://hdl.handle.net/21.15107/rcub_intor_880 .

TY  - CONF
AU  - Prijić, Ivana
AU  - Panić, Marko
AU  - Simić, Mihajlo
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Lukić, Ivana
AU  - Dragačević, Luka
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/877
AB  - Diphtheria toxin is a single polypeptide chain produced by toxigenic strains of Corynebacterium diphtheriae that causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Formaldehyde (chemical) detoxification converts diphtheria toxin into toxoid, which is used in diphtheria vaccine production. Recombinant, genetically detoxified diphtheria toxin is superior in terms of safety and purity, but it has still not found its application in recombinant diphtheria vaccine production. Both chemically and genetically inactivated forms of the diphtheria toxin have proven effective as protein carriers in conjugate vaccines. The goal of this study was to create a plasmid construct which can be used to express a genetically inactivated diphtheria toxin. Gene coding for diphtheria toxin was cloned into pMALHisEk expression vector and introduced into DH5α competent Escherichia coli cells. Three site-directed point mutations, which led to three amino acid substitutions (G52E-substitutes glycine with glutamic acid, G79D- substitutes glycine with aspartic acid, E148D- substitutes glutamic acid with aspartic acid) were conducted. A single G52E amino acid substitution is responsible for the loss of the enzymatic activity of the diphtheria toxin. G79D is recognized as a good candidate site for combining with other mutations in vaccine development and E148D may be a good candidate as carrier protein because it could reduce both the stability of NAD binding and catalytic activity of the enzyme. Each individual mutation is sufficient for toxin inactivation, but together they ensure non-toxicity, preventing reversion to the wild-type sequence. All mutations were confirmed by DNA sequencing. Recombinant diphtheria toxoid could serve as a potential vaccine epitope or protein carrier for conjugate vaccines. Further optimization of recombinant protein expression in Escherichia coli should provide sufficient quantities of soluble recombinant protein for further testing of its safety, immunogenicity and protection.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Inactivation of diphtheria toxin by site-directed mutagenesis
EP  - 115
SP  - 115
UR  - https://hdl.handle.net/21.15107/rcub_intor_877
ER  - 

@conference{
author = "Prijić, Ivana and Panić, Marko and Simić, Mihajlo and Blagojević, Veljko and Ćuruvija, Ivana and Lukić, Ivana and Dragačević, Luka and Kojić, Milan",
year = "2024",
abstract = "Diphtheria toxin is a single polypeptide chain produced by toxigenic strains of Corynebacterium diphtheriae that causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Formaldehyde (chemical) detoxification converts diphtheria toxin into toxoid, which is used in diphtheria vaccine production. Recombinant, genetically detoxified diphtheria toxin is superior in terms of safety and purity, but it has still not found its application in recombinant diphtheria vaccine production. Both chemically and genetically inactivated forms of the diphtheria toxin have proven effective as protein carriers in conjugate vaccines. The goal of this study was to create a plasmid construct which can be used to express a genetically inactivated diphtheria toxin. Gene coding for diphtheria toxin was cloned into pMALHisEk expression vector and introduced into DH5α competent Escherichia coli cells. Three site-directed point mutations, which led to three amino acid substitutions (G52E-substitutes glycine with glutamic acid, G79D- substitutes glycine with aspartic acid, E148D- substitutes glutamic acid with aspartic acid) were conducted. A single G52E amino acid substitution is responsible for the loss of the enzymatic activity of the diphtheria toxin. G79D is recognized as a good candidate site for combining with other mutations in vaccine development and E148D may be a good candidate as carrier protein because it could reduce both the stability of NAD binding and catalytic activity of the enzyme. Each individual mutation is sufficient for toxin inactivation, but together they ensure non-toxicity, preventing reversion to the wild-type sequence. All mutations were confirmed by DNA sequencing. Recombinant diphtheria toxoid could serve as a potential vaccine epitope or protein carrier for conjugate vaccines. Further optimization of recombinant protein expression in Escherichia coli should provide sufficient quantities of soluble recombinant protein for further testing of its safety, immunogenicity and protection.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Inactivation of diphtheria toxin by site-directed mutagenesis",
pages = "115-115",
url = "https://hdl.handle.net/21.15107/rcub_intor_877"
}

Prijić, I., Panić, M., Simić, M., Blagojević, V., Ćuruvija, I., Lukić, I., Dragačević, L.,& Kojić, M.. (2024). Inactivation of diphtheria toxin by site-directed mutagenesis. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 115-115.
https://hdl.handle.net/21.15107/rcub_intor_877

Prijić I, Panić M, Simić M, Blagojević V, Ćuruvija I, Lukić I, Dragačević L, Kojić M. Inactivation of diphtheria toxin by site-directed mutagenesis. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:115-115.
https://hdl.handle.net/21.15107/rcub_intor_877 .

Prijić, Ivana, Panić, Marko, Simić, Mihajlo, Blagojević, Veljko, Ćuruvija, Ivana, Lukić, Ivana, Dragačević, Luka, Kojić, Milan, "Inactivation of diphtheria toxin by site-directed mutagenesis" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):115-115,
https://hdl.handle.net/21.15107/rcub_intor_877 .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Prijić, Ivana
AU  - Radosavljević, Tatjana
AU  - Samardžić, Janko
AU  - Radosavljevic, Milica
AU  - Janković, Radmila
AU  - Djuretić, Jasmina
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/867
AB  - Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.
PB  - MDPI
T2  - Biomedicines
T2  - Biomedicines
T1  - NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats
IS  - 4
SP  - 717
VL  - 12
DO  - 10.3390/biomedicines12040717
ER  - 

@article{
author = "Bufan, Biljana and Ćuruvija, Ivana and Blagojević, Veljko and Grujić-Milanović, Jelica and Prijić, Ivana and Radosavljević, Tatjana and Samardžić, Janko and Radosavljevic, Milica and Janković, Radmila and Djuretić, Jasmina",
year = "2024",
abstract = "Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.",
publisher = "MDPI",
journal = "Biomedicines, Biomedicines",
title = "NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats",
number = "4",
pages = "717",
volume = "12",
doi = "10.3390/biomedicines12040717"
}

Bufan, B., Ćuruvija, I., Blagojević, V., Grujić-Milanović, J., Prijić, I., Radosavljević, T., Samardžić, J., Radosavljevic, M., Janković, R.,& Djuretić, J.. (2024). NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats. in Biomedicines
MDPI., 12(4), 717.
https://doi.org/10.3390/biomedicines12040717

Bufan B, Ćuruvija I, Blagojević V, Grujić-Milanović J, Prijić I, Radosavljević T, Samardžić J, Radosavljevic M, Janković R, Djuretić J. NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats. in Biomedicines. 2024;12(4):717.
doi:10.3390/biomedicines12040717 .

Bufan, Biljana, Ćuruvija, Ivana, Blagojević, Veljko, Grujić-Milanović, Jelica, Prijić, Ivana, Radosavljević, Tatjana, Samardžić, Janko, Radosavljevic, Milica, Janković, Radmila, Djuretić, Jasmina, "NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats" in Biomedicines, 12, no. 4 (2024):717,
https://doi.org/10.3390/biomedicines12040717 . .

TY  - JOUR
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Dragačević, Luka
AU  - Vujić, Vesna
AU  - Lukić, Ivana
AU  - Stanojević, Stanislava
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/693
AB  - BCG vaccination induces a memory-like response in innate immune cells known as
trained immunity. In this study, we investigated the modification of innate immune
cells by BCG vaccination in acute peritoneal inflammation. We induced peritonitis with
thioglycollate (TG) in young Albino Oxford male rats which were immunised s.c. with
a BCG vaccine (BCG group) or saline (control group) 7 days prior. Peritoneal cells were
examined for 7 days after TG injection by flow cytometry, and for NO production and
peroxidase activity. Prior in vivo BCG priming altered TG-elicited peritoneal lavage
cells as following: increased in vitro LPS and BCG stimulated NO production from total
cells compared to adherent cells (day 1); increased cell number (days 3 and 5);
increased percentage of inflammatory monocytes (SSCmidCD43lowCD11bmid) and
eosinophils (SSCHihiS48+CD43hi), and a higher level of surface CD11b expression on
CD163+ macrophages (day 5); increased in vitro LPS and BCG stimulated peroxidase
activity (days 5 and 7); and increased percentage of CD163+MHCII+ cells (day 7). On
day 7, cells from both experimental groups showed no production of NO in response to
in vitro stimulation. We conclude that BCG vaccination had a substantial effect on the
acute phase of sterile inflammation, which may lead to the later observed phenotypic
and functional changes that could be seen as accelerated resolution of inflammation
and possibly point to trained immune response.
PB  - Wiley
T1  - BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?
EP  - 127
IS  - S2
SP  - 127
VL  - 52
UR  - https://hdl.handle.net/21.15107/rcub_intor_693
ER  - 

@article{
author = "Ćuruvija, Ivana and Blagojević, Veljko and Dragačević, Luka and Vujić, Vesna and Lukić, Ivana and Stanojević, Stanislava",
year = "2022",
abstract = "BCG vaccination induces a memory-like response in innate immune cells known as
trained immunity. In this study, we investigated the modification of innate immune
cells by BCG vaccination in acute peritoneal inflammation. We induced peritonitis with
thioglycollate (TG) in young Albino Oxford male rats which were immunised s.c. with
a BCG vaccine (BCG group) or saline (control group) 7 days prior. Peritoneal cells were
examined for 7 days after TG injection by flow cytometry, and for NO production and
peroxidase activity. Prior in vivo BCG priming altered TG-elicited peritoneal lavage
cells as following: increased in vitro LPS and BCG stimulated NO production from total
cells compared to adherent cells (day 1); increased cell number (days 3 and 5);
increased percentage of inflammatory monocytes (SSCmidCD43lowCD11bmid) and
eosinophils (SSCHihiS48+CD43hi), and a higher level of surface CD11b expression on
CD163+ macrophages (day 5); increased in vitro LPS and BCG stimulated peroxidase
activity (days 5 and 7); and increased percentage of CD163+MHCII+ cells (day 7). On
day 7, cells from both experimental groups showed no production of NO in response to
in vitro stimulation. We conclude that BCG vaccination had a substantial effect on the
acute phase of sterile inflammation, which may lead to the later observed phenotypic
and functional changes that could be seen as accelerated resolution of inflammation
and possibly point to trained immune response.",
publisher = "Wiley",
title = "BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?",
pages = "127-127",
number = "S2",
volume = "52",
url = "https://hdl.handle.net/21.15107/rcub_intor_693"
}

Ćuruvija, I., Blagojević, V., Dragačević, L., Vujić, V., Lukić, I.,& Stanojević, S.. (2022). BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?. 
Wiley., 52(S2), 127-127.
https://hdl.handle.net/21.15107/rcub_intor_693

Ćuruvija I, Blagojević V, Dragačević L, Vujić V, Lukić I, Stanojević S. BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?. 2022;52(S2):127-127.
https://hdl.handle.net/21.15107/rcub_intor_693 .

Ćuruvija, Ivana, Blagojević, Veljko, Dragačević, Luka, Vujić, Vesna, Lukić, Ivana, Stanojević, Stanislava, "BCG vaccination induced alterations of thioglycollate-elicited peritoneal phagocytes: a case of trained immunity?", 52, no. S2 (2022):127-127,
https://hdl.handle.net/21.15107/rcub_intor_693 .

TY  - CONF
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Dragačević, Luka
AU  - Vujić, Vesna
AU  - Lukić, Ivana
AU  - Stanojević, Stanislava
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/694
AB  - Inflammation is a redistribution of immune cells, providing a more efficient elimination of the inflammatory offense. However, it is not limited to local microenvironment. In this study, the interaction of the effect of BCG priming and peritoneal inflammation on the remote inflammatory milieu of infected lung was investigated. Young male AO rats infected with Mycoplasma spp. were s.c. injected with BCG (3x105 CFU) or saline, and 7 days later received an i.p. injection of 7ml of thioglycollate (TG) or saline. Up to 7 days after TG injection, a broncho-alveolar lavage (BAL) was performed, and cells were analysed for their surface marker expression and NO production. Infected rats had a high percentage of HIS48HiCD11bHi neutrophils. BCG priming didn’t alter BAL cells phenotype, while TG injection increased the proportion of MHCII+CD11blow activated alveolar macrophages (aAMFs) on day 7. However, the BCG+TG group showed significant changes – percentage of HIS48HiCD11bHi neutrophils decreased from day 3, the share of aAMFs increased from day 5 and the share of MHCII+CD11b-AMFs increased on days 3-5. However, the percentage of B220+FSClow B lymphocytes were increased from day 1. Production of NO from BAL fluid cells was low in all groups. We conclude that BCG vaccination likely increased the number of circulating B lymphocytes, while TG-induced peritoneal inflammation potentially prevented their entry into the peritoneal cavity, forcing them into permissive tissues, such as lungs.
PB  - Wiley
T1  - Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation
EP  - 55
IS  - S2
SP  - 55
VL  - 52
UR  - https://hdl.handle.net/21.15107/rcub_intor_694
ER  - 

@conference{
author = "Blagojević, Veljko and Ćuruvija, Ivana and Dragačević, Luka and Vujić, Vesna and Lukić, Ivana and Stanojević, Stanislava",
year = "2022",
abstract = "Inflammation is a redistribution of immune cells, providing a more efficient elimination of the inflammatory offense. However, it is not limited to local microenvironment. In this study, the interaction of the effect of BCG priming and peritoneal inflammation on the remote inflammatory milieu of infected lung was investigated. Young male AO rats infected with Mycoplasma spp. were s.c. injected with BCG (3x105 CFU) or saline, and 7 days later received an i.p. injection of 7ml of thioglycollate (TG) or saline. Up to 7 days after TG injection, a broncho-alveolar lavage (BAL) was performed, and cells were analysed for their surface marker expression and NO production. Infected rats had a high percentage of HIS48HiCD11bHi neutrophils. BCG priming didn’t alter BAL cells phenotype, while TG injection increased the proportion of MHCII+CD11blow activated alveolar macrophages (aAMFs) on day 7. However, the BCG+TG group showed significant changes – percentage of HIS48HiCD11bHi neutrophils decreased from day 3, the share of aAMFs increased from day 5 and the share of MHCII+CD11b-AMFs increased on days 3-5. However, the percentage of B220+FSClow B lymphocytes were increased from day 1. Production of NO from BAL fluid cells was low in all groups. We conclude that BCG vaccination likely increased the number of circulating B lymphocytes, while TG-induced peritoneal inflammation potentially prevented their entry into the peritoneal cavity, forcing them into permissive tissues, such as lungs.",
publisher = "Wiley",
title = "Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation",
pages = "55-55",
number = "S2",
volume = "52",
url = "https://hdl.handle.net/21.15107/rcub_intor_694"
}

Blagojević, V., Ćuruvija, I., Dragačević, L., Vujić, V., Lukić, I.,& Stanojević, S.. (2022). Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation. 
Wiley., 52(S2), 55-55.
https://hdl.handle.net/21.15107/rcub_intor_694

Blagojević V, Ćuruvija I, Dragačević L, Vujić V, Lukić I, Stanojević S. Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation. 2022;52(S2):55-55.
https://hdl.handle.net/21.15107/rcub_intor_694 .

Blagojević, Veljko, Ćuruvija, Ivana, Dragačević, Luka, Vujić, Vesna, Lukić, Ivana, Stanojević, Stanislava, "Modifying Mycoplasma-infected lung immune cells through an intriguing interplay of BCG priming and peritoneal inflammation", 52, no. S2 (2022):55-55,
https://hdl.handle.net/21.15107/rcub_intor_694 .

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Bufan, Biljana
AU  - Đorović, Emilija
AU  - Blagojević, Veljko
AU  - Grujić-Milanović, Jelica
AU  - Marković, Milica
AU  - Djuretić, Jasmina
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/674
AB  - Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats.
C3  - FENS Forum Book of Abstracts, Paris
T1  - Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis
SP  - S05-250
UR  - https://hdl.handle.net/21.15107/rcub_intor_674
ER  - 

@conference{
author = "Ćuruvija, Ivana and Bufan, Biljana and Đorović, Emilija and Blagojević, Veljko and Grujić-Milanović, Jelica and Marković, Milica and Djuretić, Jasmina",
year = "2022",
abstract = "Aims Ageing affects N-methyl-D-aspartate receptors (NMDARs), their expression and function in neuronal and non-neuronal
cells. Contribution of NMDARs to pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been investigated
but further study is still needed. The aim of this study was to determine whether ageing affects the role of NMDARs in EAE.
Methods Memantine, a non-competitive NMDAR antagonist which limits pathological activity of NMDARs while sparing
normal synaptic activity, was administered orally from day 7 after immunization to 3- and 24-month-old female Dark Agouti
rats. The animals were sacrificed at the peak of the disease. Spinal cord mononuclear cells were analyzed by flow cytometry.
Brain tissue was collected for biochemical analysis of redox status and RT-qPCR. Results Semiprophylactic administration of
memantine ameliorated clinical disease course, with greater effect in aged rats. Memantine reduced the number, frequency,
and reactivation of CD4+ T lymphocytes and increased the relative percentage of CX3CR1-expressing microglia in spinal
cord, but to a greater extent in aged rats. Additionally, analysis of brain redox status parameters showed that memantine was
more effective in reducing superoxide anion radical, malondialdehyde and advanced oxidation protein products in aged rats
than in young ones. In accordance with previous findings, NMDAR inhibition by memantine decreased NADPH oxidase and
IL-1β expression and increased the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 expression, to a greater
extent in aged rats. Conclusions The involvement of NMDARs in the pathogenesis of EAE was age-dependent, being more
pronounced in aged than in young rats.",
journal = "FENS Forum Book of Abstracts, Paris",
title = "Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis",
pages = "S05-250",
url = "https://hdl.handle.net/21.15107/rcub_intor_674"
}

Ćuruvija, I., Bufan, B., Đorović, E., Blagojević, V., Grujić-Milanović, J., Marković, M.,& Djuretić, J.. (2022). Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis. in FENS Forum Book of Abstracts, Paris, S05-250.
https://hdl.handle.net/21.15107/rcub_intor_674

Ćuruvija I, Bufan B, Đorović E, Blagojević V, Grujić-Milanović J, Marković M, Djuretić J. Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis. in FENS Forum Book of Abstracts, Paris. 2022;:S05-250.
https://hdl.handle.net/21.15107/rcub_intor_674 .

Ćuruvija, Ivana, Bufan, Biljana, Đorović, Emilija, Blagojević, Veljko, Grujić-Milanović, Jelica, Marković, Milica, Djuretić, Jasmina, "Age-Dependent Role Of Nmda Receptors In Experimental Autoimmune Encephalomyelitis" in FENS Forum Book of Abstracts, Paris (2022):S05-250,
https://hdl.handle.net/21.15107/rcub_intor_674 .

TY  - CONF
AU  - Kovačević Jovanović, Vesna
AU  - Ćuruvija, Ivana
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/673
AB  - BACKGROUND A variety of commensal bacterial taxa elicit serum IgA responses resulting in protection against polymicrobial sepsis, whereas anti-commensal IgG may have deleterious role in gastrointestinal and systemic inflammation. OBJECTIVES The aim was to determine the systemic levels of specific antibodies directed to autologous E.coli in rats of Albino Oxford (AO) and Dark Agouti (DA) rat strains during colitis. METHODS Rats were intrarectally injected with ethanol or trinitrobenzenesulfonic acid (TNBS, 10 or 40mg/kg) whereas controls received saline in the same manner. Sera were tested for the level of anti-E.coli antibodies of IgG1, IgG2a, IgG2b and IgA classes by ELISA. RESULTS Both rat strains developed colitis, but the degree of colon necrosis and hyperemia were slightly greater in DA than in AO rats and the survival rate was significantly lower in DA relative to AO rats. Among saline-treated controls, the levels of IgG1, IgG2a, and IgG2b anti-E.coli antibodies were comparable between rat strains, whereas the amounts of IgA were significantly higher in DA compared to AO rats. Development of colitis significantly increased the amount of anti-E.coli antibodies of IgA and IgG2a classes in sera of AO rats, and those of IgG2a and IgG2b classes in sera of DA rats. Hence, mostly beneficial role of IgA and probably deleterious role of IgG2b antibodies directed to commensal E.coli during colitis may be suggested, whereas the role of anti-E.coli antibodies of IgG2a classes remains intriguing.
PB  - Serbian Society of Microbiology
C3  - FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia
T1  - The intriguing role of anti-commensal bacteria antibodies in sera of colitic rats
SP  - 883
SP  - 883
SP  - 1538
UR  - https://hdl.handle.net/21.15107/rcub_intor_673
ER  - 

@conference{
author = "Kovačević Jovanović, Vesna and Ćuruvija, Ivana and Stanojević, Stanislava and Blagojević, Veljko",
year = "2022",
abstract = "BACKGROUND A variety of commensal bacterial taxa elicit serum IgA responses resulting in protection against polymicrobial sepsis, whereas anti-commensal IgG may have deleterious role in gastrointestinal and systemic inflammation. OBJECTIVES The aim was to determine the systemic levels of specific antibodies directed to autologous E.coli in rats of Albino Oxford (AO) and Dark Agouti (DA) rat strains during colitis. METHODS Rats were intrarectally injected with ethanol or trinitrobenzenesulfonic acid (TNBS, 10 or 40mg/kg) whereas controls received saline in the same manner. Sera were tested for the level of anti-E.coli antibodies of IgG1, IgG2a, IgG2b and IgA classes by ELISA. RESULTS Both rat strains developed colitis, but the degree of colon necrosis and hyperemia were slightly greater in DA than in AO rats and the survival rate was significantly lower in DA relative to AO rats. Among saline-treated controls, the levels of IgG1, IgG2a, and IgG2b anti-E.coli antibodies were comparable between rat strains, whereas the amounts of IgA were significantly higher in DA compared to AO rats. Development of colitis significantly increased the amount of anti-E.coli antibodies of IgA and IgG2a classes in sera of AO rats, and those of IgG2a and IgG2b classes in sera of DA rats. Hence, mostly beneficial role of IgA and probably deleterious role of IgG2b antibodies directed to commensal E.coli during colitis may be suggested, whereas the role of anti-E.coli antibodies of IgG2a classes remains intriguing.",
publisher = "Serbian Society of Microbiology",
journal = "FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia",
title = "The intriguing role of anti-commensal bacteria antibodies in sera of colitic rats",
pages = "883-883-1538",
url = "https://hdl.handle.net/21.15107/rcub_intor_673"
}

Kovačević Jovanović, V., Ćuruvija, I., Stanojević, S.,& Blagojević, V.. (2022). The intriguing role of anti-commensal bacteria antibodies in sera of colitic rats. in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia
Serbian Society of Microbiology., 883.
https://hdl.handle.net/21.15107/rcub_intor_673

Kovačević Jovanović V, Ćuruvija I, Stanojević S, Blagojević V. The intriguing role of anti-commensal bacteria antibodies in sera of colitic rats. in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia. 2022;:883.
https://hdl.handle.net/21.15107/rcub_intor_673 .

Kovačević Jovanović, Vesna, Ćuruvija, Ivana, Stanojević, Stanislava, Blagojević, Veljko, "The intriguing role of anti-commensal bacteria antibodies in sera of colitic rats" in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia (2022):883,
https://hdl.handle.net/21.15107/rcub_intor_673 .

TY  - CONF
AU  - Kovačević Jovanović, Vesna
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Stanojević, Stanislava
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/672
AB  - BACKGROUND Deregulation of the immune response to microbiota or pathogens, and increased intestinal permeability have been proposed as disease-driving mechanisms in colitis. Since peritoneal macrophages guard the sterility of peritoneal cavity from bacterial leakage from the gut, it is plausible to assume that peritoneal macrophages are involved in colitis development. OBJECTIVES The objective was to investigate changes in the composition of peritoneal cells and their response to stimulation by selected gut microbiota during colitis. METHODS Seven days following induction of colitis with intrarectal instillation of ethanol or trinitrobenzenesulfonic acid (TNBS, 10mg/kg or 40mg/kg), peritoneal cells of Dark Agouti (DA) rats were isolated and subjected to flow cytometry. The amount of IL-6 and TNF-α produced by adherent cells was determined by ELISA following in vitro stimulation with LPS and commensal E.coli and Enteroccocus spp.
RESULTS
Instillation of ethanol or TNBS (10 and 40 mg/kg) increased the proportion of CD11bintCD4low monocytes
and decreased the proportion of resident CD163+MHCIIIo macrophages and CD163-MHCIIhi macrophage/dendritic cells.
In vitro treatment with Enterococcus spp. was superior over LPS and E.coli in increasing macrophage TNF-α release in all
but saline-injected control rats. In vitro treatment with E.coli exceeded the level of LPS stimulation in
inducing macrophage IL-6 release in saline- and ethanol-injected rats. It may be concluded that changes in the
composition of peritoneal cells during colitis and, subsequently, their selectively altered response to gut commensals
may perpetuate or modulate inflammation during disease development
PB  - Serbian Society of Microbiology
C3  - FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia
T1  - Changes in the composition of rat peritoneal cells and their response to stimulation by selected gut microbiota during colitis
SP  - 880
SP  - 880
SP  - 1536
UR  - https://hdl.handle.net/21.15107/rcub_intor_672
ER  - 

@conference{
author = "Kovačević Jovanović, Vesna and Blagojević, Veljko and Ćuruvija, Ivana and Stanojević, Stanislava",
year = "2022",
abstract = "BACKGROUND Deregulation of the immune response to microbiota or pathogens, and increased intestinal permeability have been proposed as disease-driving mechanisms in colitis. Since peritoneal macrophages guard the sterility of peritoneal cavity from bacterial leakage from the gut, it is plausible to assume that peritoneal macrophages are involved in colitis development. OBJECTIVES The objective was to investigate changes in the composition of peritoneal cells and their response to stimulation by selected gut microbiota during colitis. METHODS Seven days following induction of colitis with intrarectal instillation of ethanol or trinitrobenzenesulfonic acid (TNBS, 10mg/kg or 40mg/kg), peritoneal cells of Dark Agouti (DA) rats were isolated and subjected to flow cytometry. The amount of IL-6 and TNF-α produced by adherent cells was determined by ELISA following in vitro stimulation with LPS and commensal E.coli and Enteroccocus spp.
RESULTS
Instillation of ethanol or TNBS (10 and 40 mg/kg) increased the proportion of CD11bintCD4low monocytes
and decreased the proportion of resident CD163+MHCIIIo macrophages and CD163-MHCIIhi macrophage/dendritic cells.
In vitro treatment with Enterococcus spp. was superior over LPS and E.coli in increasing macrophage TNF-α release in all
but saline-injected control rats. In vitro treatment with E.coli exceeded the level of LPS stimulation in
inducing macrophage IL-6 release in saline- and ethanol-injected rats. It may be concluded that changes in the
composition of peritoneal cells during colitis and, subsequently, their selectively altered response to gut commensals
may perpetuate or modulate inflammation during disease development",
publisher = "Serbian Society of Microbiology",
journal = "FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia",
title = "Changes in the composition of rat peritoneal cells and their response to stimulation by selected gut microbiota during colitis",
pages = "880-880-1536",
url = "https://hdl.handle.net/21.15107/rcub_intor_672"
}

Kovačević Jovanović, V., Blagojević, V., Ćuruvija, I.,& Stanojević, S.. (2022). Changes in the composition of rat peritoneal cells and their response to stimulation by selected gut microbiota during colitis. in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia
Serbian Society of Microbiology., 880.
https://hdl.handle.net/21.15107/rcub_intor_672

Kovačević Jovanović V, Blagojević V, Ćuruvija I, Stanojević S. Changes in the composition of rat peritoneal cells and their response to stimulation by selected gut microbiota during colitis. in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia. 2022;:880.
https://hdl.handle.net/21.15107/rcub_intor_672 .

Kovačević Jovanović, Vesna, Blagojević, Veljko, Ćuruvija, Ivana, Stanojević, Stanislava, "Changes in the composition of rat peritoneal cells and their response to stimulation by selected gut microbiota during colitis" in FEMS conference on microbiology in association with Serbian Society of Microbiology, 30 June - 2 July, Serbia (2022):880,
https://hdl.handle.net/21.15107/rcub_intor_672 .

TY  - JOUR
AU  - Nikodijević, Slavomir
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Kosanović, Dejana
AU  - Đukić, Tamara
AU  - Đorđević, Brižita
AU  - Ilić, Vesna
AU  - Minić, Rajna
PY  - 2022
UR  - http://intor.torlakinstitut.com/handle/123456789/632
AB  - Increased interest in microbiota calls for the thorough analysis of antibody reactivity to different microorganisms. As salivary IgA represents the first line of defence against microorganisms contacting mucosal surfaces, we explored the binding and specificity of salivary IgA by testing the binding of purified, FITC-labelled salivary IgA to different microorganisms in flow cytometry and conclude that this kind of analysis enables the differentiation of species/strains with high IgA binding capacity, which should be corroborated on a larger sample size. Further we compare, with in-house ELISA, the binding of polyclonal salivary IgA with the binding of polyclonal serum IgA from the same individuals to whole microbial cells and to purified microbial components. High correlations were obtained in total salivary IgA binding to Lactobacillus rhamnosus and Escherichia coli, very distant bacterial species, as well as to isolated bacterial components (r = .70–.97). The binding of total salivary IgA resembled the binding of both salivary IgA1 and IgA2, with IgA2 predominating. For serum polyclonal IgA repertoire, substantially higher specificity was obtained. Serum IgA binding to E. coli correlated best with serum IgA binding to lipopolysaccharide (r = .86), and serum IgA against L. rhamnosus correlated best with the anti-peptidoglycan IgA levels (r = .88). We have also detected that total serum IgA response is governed by either IgA1 or IgA2 response, depending on the nature of the antigen/s. We conclude that steady state salivary IgA repertoire, unlike serum IgA repertoire, consists of polyreactive antibodies with innate specificity, questioning its capacity to select resident microbiota.
PB  - The Scandinavian Foundation for Immunology
T2  - Scandinavian Journal of Immunology
T1  - Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans
VL  - 96
DO  - 10.1111/sji.13223
ER  - 

@article{
author = "Nikodijević, Slavomir and Blagojević, Veljko and Ćuruvija, Ivana and Kosanović, Dejana and Đukić, Tamara and Đorđević, Brižita and Ilić, Vesna and Minić, Rajna",
year = "2022",
abstract = "Increased interest in microbiota calls for the thorough analysis of antibody reactivity to different microorganisms. As salivary IgA represents the first line of defence against microorganisms contacting mucosal surfaces, we explored the binding and specificity of salivary IgA by testing the binding of purified, FITC-labelled salivary IgA to different microorganisms in flow cytometry and conclude that this kind of analysis enables the differentiation of species/strains with high IgA binding capacity, which should be corroborated on a larger sample size. Further we compare, with in-house ELISA, the binding of polyclonal salivary IgA with the binding of polyclonal serum IgA from the same individuals to whole microbial cells and to purified microbial components. High correlations were obtained in total salivary IgA binding to Lactobacillus rhamnosus and Escherichia coli, very distant bacterial species, as well as to isolated bacterial components (r = .70–.97). The binding of total salivary IgA resembled the binding of both salivary IgA1 and IgA2, with IgA2 predominating. For serum polyclonal IgA repertoire, substantially higher specificity was obtained. Serum IgA binding to E. coli correlated best with serum IgA binding to lipopolysaccharide (r = .86), and serum IgA against L. rhamnosus correlated best with the anti-peptidoglycan IgA levels (r = .88). We have also detected that total serum IgA response is governed by either IgA1 or IgA2 response, depending on the nature of the antigen/s. We conclude that steady state salivary IgA repertoire, unlike serum IgA repertoire, consists of polyreactive antibodies with innate specificity, questioning its capacity to select resident microbiota.",
publisher = "The Scandinavian Foundation for Immunology",
journal = "Scandinavian Journal of Immunology",
title = "Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans",
volume = "96",
doi = "10.1111/sji.13223"
}

Nikodijević, S., Blagojević, V., Ćuruvija, I., Kosanović, D., Đukić, T., Đorđević, B., Ilić, V.,& Minić, R.. (2022). Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans. in Scandinavian Journal of Immunology
The Scandinavian Foundation for Immunology., 96.
https://doi.org/10.1111/sji.13223

Nikodijević S, Blagojević V, Ćuruvija I, Kosanović D, Đukić T, Đorđević B, Ilić V, Minić R. Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans. in Scandinavian Journal of Immunology. 2022;96.
doi:10.1111/sji.13223 .

Nikodijević, Slavomir, Blagojević, Veljko, Ćuruvija, Ivana, Kosanović, Dejana, Đukić, Tamara, Đorđević, Brižita, Ilić, Vesna, Minić, Rajna, "Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans" in Scandinavian Journal of Immunology, 96 (2022),
https://doi.org/10.1111/sji.13223 . .

TY  - CONF
AU  - Blagojević, Veljko
AU  - Vujić, Vesna
AU  - Ćuruvija, Ivana
AU  - Veljović, Katarina
AU  - Soković Bajić, Svetlana
AU  - Stanojević, Stanislava
PY  - 2021
UR  - http://intor.torlakinstitut.com/handle/123456789/667
AB  - We tested the effects of early‐life probiotic treatment on the induction of colitis in female and male adult rats. Rat pups were fed an aqueous solution of Lactobacillus rhamnosus (from 
day 4  to day 30). Feces were collected  for microbial analysis. Colitis was induced at day 85. Seven days later  rats were graded  for histological damage in colon, and samples of 
mesenteric lymph node (MLN) and peritoneal exudate cells were analyzed. Female rats developed slightly less severe symptoms of colitis than males, whereas early‐life probiotic 
treatment had a more pronounced effect on males in nearly every analyzed parameter. Namely, it increased fecal bacterial diversity and ameliorated colon tissue damage, as well 
as increased percentage of resident peritoneal macrophages (CD163+), decreased peritoneal monocyte (HIS48+CD43+) influx, reduced production of IFNγ and IL10 by MLN cells, 
attenuated NO production in stimulated peritoneal macrophages and unstimulated MLN cells of male rats. Our findings reveal that effects of probiotic treatment are sex‐specific to an 
extent. While microbial diversity was impacted by probiotic treatment in both sexes at an early age, the effect was more pronounced in young males, and it lasted to their adulthood. 
The change in microbial diversity correlated with improved outcome of TNBS‐induced colitis, confirming the importance of microbiota for local inflammatory processes. It remains to 
be elucidated whether the sex differences in the effect of probiotic treatment on development of colitis may be a consequence of sex differences in early‐life microbial diversity and 
severity of colitis symptoms in untreated rats.
PB  - Wiley
C3  - European Journal of Immunology
T1  - Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats
EP  - 311
SP  - 311
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_intor_667
ER  - 

@conference{
author = "Blagojević, Veljko and Vujić, Vesna and Ćuruvija, Ivana and Veljović, Katarina and Soković Bajić, Svetlana and Stanojević, Stanislava",
year = "2021",
abstract = "We tested the effects of early‐life probiotic treatment on the induction of colitis in female and male adult rats. Rat pups were fed an aqueous solution of Lactobacillus rhamnosus (from 
day 4  to day 30). Feces were collected  for microbial analysis. Colitis was induced at day 85. Seven days later  rats were graded  for histological damage in colon, and samples of 
mesenteric lymph node (MLN) and peritoneal exudate cells were analyzed. Female rats developed slightly less severe symptoms of colitis than males, whereas early‐life probiotic 
treatment had a more pronounced effect on males in nearly every analyzed parameter. Namely, it increased fecal bacterial diversity and ameliorated colon tissue damage, as well 
as increased percentage of resident peritoneal macrophages (CD163+), decreased peritoneal monocyte (HIS48+CD43+) influx, reduced production of IFNγ and IL10 by MLN cells, 
attenuated NO production in stimulated peritoneal macrophages and unstimulated MLN cells of male rats. Our findings reveal that effects of probiotic treatment are sex‐specific to an 
extent. While microbial diversity was impacted by probiotic treatment in both sexes at an early age, the effect was more pronounced in young males, and it lasted to their adulthood. 
The change in microbial diversity correlated with improved outcome of TNBS‐induced colitis, confirming the importance of microbiota for local inflammatory processes. It remains to 
be elucidated whether the sex differences in the effect of probiotic treatment on development of colitis may be a consequence of sex differences in early‐life microbial diversity and 
severity of colitis symptoms in untreated rats.",
publisher = "Wiley",
journal = "European Journal of Immunology",
title = "Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats",
pages = "311-311",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_intor_667"
}

Blagojević, V., Vujić, V., Ćuruvija, I., Veljović, K., Soković Bajić, S.,& Stanojević, S.. (2021). Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats. in European Journal of Immunology
Wiley., 51, 311-311.
https://hdl.handle.net/21.15107/rcub_intor_667

Blagojević V, Vujić V, Ćuruvija I, Veljović K, Soković Bajić S, Stanojević S. Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats. in European Journal of Immunology. 2021;51:311-311.
https://hdl.handle.net/21.15107/rcub_intor_667 .

Blagojević, Veljko, Vujić, Vesna, Ćuruvija, Ivana, Veljović, Katarina, Soković Bajić, Svetlana, Stanojević, Stanislava, "Sex differences in the effects of early‐life probiotic treatment on TNBS‐induced colitis in rats" in European Journal of Immunology, 51 (2021):311-311,
https://hdl.handle.net/21.15107/rcub_intor_667 .

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Vujić, Vesna
PY  - 2021
UR  - http://intor.torlakinstitut.com/handle/123456789/611
AB  - Gut microbiota contribute to shaping the immune repertoire of the host, whereas probiotics may exert beneficial effects by modulating immune responses. Having in mind the differences in both the composition of gut microbiota and the immune response between rats of Albino Oxford (AO) and Dark Agouti (DA) rat strains, we investigated if intraperitoneal (i.p.) injection of live Lactobacillus rhamnosus (LB) may influence peri-toneal cavity cell response to invitro treatments with selected microbiota in the rat strain-dependent manner. Peritoneal cavity cells from AO and DA rats were lavaged two (d2) and seven days (d7) following i.p. injection with LB and tested for NO, urea, and H2O2 release basally, or upon invitro stimulation with autologous E.coli and Enterococcus spp. Whereas the single i.p. injection of LB nearly depleted resident macrophages and increased the proportion of small inflammatory macrophages and monocytes on d2 in both rat strains, greater proportion of MHCIIhiCD163− and CCR7+ cells and increased NO/diminished H2O2 release in DA compared with AO rats suggest a more intense inflammatory prim-ing by LB in this rat strain. Even though E.coli- and/or Enterococcus spp.-induced rise in H2O2 release invitro was abrogated by LB in cells from both rat strains, LB prevented microbiota-induced increase in NO/urea ratio only in cells from AO and augmented it in cells from DA rats. Thus, the immunomodulatory properties may not be constant for particular probiotic bacteria, but shaped by innate immunity of the host.
PB  - Springer Nature
T2  - Inflammation
T1  - Lactobacillus rhamnosus Affects Rat Peritoneal Cavity Cell Response to Stimulation with Gut Microbiota: Focus on the Host Innate Immunity
DO  - 10.1007/s10753-021-01513-z
ER  - 

@article{
author = "Stanojević, Stanislava and Blagojević, Veljko and Ćuruvija, Ivana and Vujić, Vesna",
year = "2021",
abstract = "Gut microbiota contribute to shaping the immune repertoire of the host, whereas probiotics may exert beneficial effects by modulating immune responses. Having in mind the differences in both the composition of gut microbiota and the immune response between rats of Albino Oxford (AO) and Dark Agouti (DA) rat strains, we investigated if intraperitoneal (i.p.) injection of live Lactobacillus rhamnosus (LB) may influence peri-toneal cavity cell response to invitro treatments with selected microbiota in the rat strain-dependent manner. Peritoneal cavity cells from AO and DA rats were lavaged two (d2) and seven days (d7) following i.p. injection with LB and tested for NO, urea, and H2O2 release basally, or upon invitro stimulation with autologous E.coli and Enterococcus spp. Whereas the single i.p. injection of LB nearly depleted resident macrophages and increased the proportion of small inflammatory macrophages and monocytes on d2 in both rat strains, greater proportion of MHCIIhiCD163− and CCR7+ cells and increased NO/diminished H2O2 release in DA compared with AO rats suggest a more intense inflammatory prim-ing by LB in this rat strain. Even though E.coli- and/or Enterococcus spp.-induced rise in H2O2 release invitro was abrogated by LB in cells from both rat strains, LB prevented microbiota-induced increase in NO/urea ratio only in cells from AO and augmented it in cells from DA rats. Thus, the immunomodulatory properties may not be constant for particular probiotic bacteria, but shaped by innate immunity of the host.",
publisher = "Springer Nature",
journal = "Inflammation",
title = "Lactobacillus rhamnosus Affects Rat Peritoneal Cavity Cell Response to Stimulation with Gut Microbiota: Focus on the Host Innate Immunity",
doi = "10.1007/s10753-021-01513-z"
}

Stanojević, S., Blagojević, V., Ćuruvija, I.,& Vujić, V.. (2021). Lactobacillus rhamnosus Affects Rat Peritoneal Cavity Cell Response to Stimulation with Gut Microbiota: Focus on the Host Innate Immunity. in Inflammation
Springer Nature..
https://doi.org/10.1007/s10753-021-01513-z

Stanojević S, Blagojević V, Ćuruvija I, Vujić V. Lactobacillus rhamnosus Affects Rat Peritoneal Cavity Cell Response to Stimulation with Gut Microbiota: Focus on the Host Innate Immunity. in Inflammation. 2021;.
doi:10.1007/s10753-021-01513-z .

Stanojević, Stanislava, Blagojević, Veljko, Ćuruvija, Ivana, Vujić, Vesna, "Lactobacillus rhamnosus Affects Rat Peritoneal Cavity Cell Response to Stimulation with Gut Microbiota: Focus on the Host Innate Immunity" in Inflammation (2021),
https://doi.org/10.1007/s10753-021-01513-z . .

TY  - THES
AU  - Ćuruvija, Ivana D.
PY  - 2021
UR  - http://intor.torlakinstitut.com/handle/123456789/619
AB  - Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl. „inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga (Mϕ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu” rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bili da se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresija markera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza, sinteza inflamatornih medijatora) Mϕ “mirne” i inflamirane (delovanjem tioglikolata) peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora za reproduktivnim starenjem uslovljene promene peritonealnih Mϕ od značaja za uspešnu rezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednom analizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacova kojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanja estradiola na Mϕ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) se sposobnost Mϕ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja već tokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mϕ sredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazuju svojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polno specifične (Mϕ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da “kontrolišu” inflamaciju od Mϕ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih za sposobnost Mϕ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imaju promene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da su za uzrasno zavisne promene u sposobnosti Mϕ da “kontrolišu” inflamaciju pored promene u koncentraciji estradiola važne i one u samim Mϕ, koje menjaju njihov odgovor na delovanje estradiola.
AB  - Aging is associated with the development of systemic, sterile chronic inflammation ("inflammaging"). Little is known about the influence of genetic factors and sex on the ability of macrophages (Mϕ), as key innate immune cells, to "control" the resolution of acute inflammation and thus the development of chronic inflammation during aging. The objectives of this dissertation were to examine 1) the influence of the early phase of reproductive aging on phenotypic characteristics (expression of markers associated with activation and origin/function) and functional characteristics (phagocytosis, synthesis of inflammatory mediators) of Mϕ isolated from “naive” and inflamed (thioglycollate-induced) peritoneal cavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors for reproductive aging-related changes of peritoneal Mϕ, especially those important for successful resolution of acute inflammation and 3) the role of sex steroids in the occurrence of these changes by comparative analysis in males and females of AO rats, their analysis in female AO rats whose ovaries were removed at the end of the reproductive period and by examining in vitro effect of estradiol on Mϕ from young and middle-aged female AO rats. The results showed that: 1) the ability of Mϕ from AO females to “control” the resolution of acute inflammation changes during the early phase of reproductive aging, and these changes are strain-specific (Mϕ from middle-aged AO females that “age more successful” than Dark Agouti females, show properties which may be associated with better "control" of inflammation); 2) these changes are sex-specific (Mϕ from middle-aged females have a greater capacity to “control” inflammation than Mϕ from males of the same age group) and 3) both estradiol and progesterone play important roles in the ability of Mϕ from AO females to “control” acute inflammation. In vitro studies revealed that, in addition to changes in estradiol concentration, intrinsic changes in Mϕ that regulate their response to estradiol action are important for agedependent changes in Mϕ ability to „control“ inflammation.
PB  - Univerzitet u Beogradu, Farmaceutski fakultet
T2  - Univerzitet u Beogradu
T1  - Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju
UR  - https://hdl.handle.net/21.15107/rcub_intor_619
ER  - 

@phdthesis{
author = "Ćuruvija, Ivana D.",
year = "2021",
abstract = "Starenje se povezuje sa razvojem sistemskog, sterilnog hroničnog zapaljenja (engl. „inflammaging”). Malo je podataka o uticaju genetskih faktora i pola na sposobnost makrofaga (Mϕ), kao ključnih ćelija urođenog imunskog odgovora, da tokom starenja “kontrolišu” rezoluciju akutnog zapaljenja i time razvoj hroničnog zapaljenja. Ciljevi ove disertacije su bili da se ispita 1) uticaj rane faze reproduktivnog starenja na fenotipske osobine (ekspresija markera povezanih sa aktivacijom i poreklom/funkcijom) i funkcijska svojstva (fagocitoza, sinteza inflamatornih medijatora) Mϕ “mirne” i inflamirane (delovanjem tioglikolata) peritonealne duplje ženki Albino Oxford (AO) pacova, 2) značaj genetskih faktora za reproduktivnim starenjem uslovljene promene peritonealnih Mϕ od značaja za uspešnu rezoluciju akutnog zapaljenja i 3) uloga polnih steroida u nastanku ovih promena uporednom analizom promena kod mužjaka i ženki AO pacova, njihovom analizom kod ženki AO pacova kojima su na kraju reproduktivnog perioda uklonjeni jajnici i ispitivanjem delovanja estradiola na Mϕ mladih i sredovečnih ženki AO pacova in vitro. Rezultati su pokazali da: 1) se sposobnost Mϕ ženki AO pacova da “kontrolišu” rezoluciju akutnog zapaljenja menja već tokom rane faze reproduktivnog starenja, kao i da su ove promene sojno specifične (Mϕ sredovečnih ženki AO pacova koje “uspešnije” stare od ženki Dark Agouti pacova pokazuju svojstva koja se mogu povezati sa boljom “kontrolom” inflamacije); 2) su ove promene polno specifične (Mϕ sredovečnih ženki imaju svojstva koja ukazuju na veći kapacitet da “kontrolišu” inflamaciju od Mϕ mužjaka istog uzrasta) i 3) u nastanku promena relevantnih za sposobnost Mϕ ženki AO pacova da “kontrolišu” akutnu inflamaciju važnu ulogu imaju promene u delovanju i estradiola i progesterona. Dodatno, ispitavanja in vitro su ukazala da su za uzrasno zavisne promene u sposobnosti Mϕ da “kontrolišu” inflamaciju pored promene u koncentraciji estradiola važne i one u samim Mϕ, koje menjaju njihov odgovor na delovanje estradiola., Aging is associated with the development of systemic, sterile chronic inflammation ("inflammaging"). Little is known about the influence of genetic factors and sex on the ability of macrophages (Mϕ), as key innate immune cells, to "control" the resolution of acute inflammation and thus the development of chronic inflammation during aging. The objectives of this dissertation were to examine 1) the influence of the early phase of reproductive aging on phenotypic characteristics (expression of markers associated with activation and origin/function) and functional characteristics (phagocytosis, synthesis of inflammatory mediators) of Mϕ isolated from “naive” and inflamed (thioglycollate-induced) peritoneal cavity of females Albino Oxford (AO) rats; 2) the significance of genetic factors for reproductive aging-related changes of peritoneal Mϕ, especially those important for successful resolution of acute inflammation and 3) the role of sex steroids in the occurrence of these changes by comparative analysis in males and females of AO rats, their analysis in female AO rats whose ovaries were removed at the end of the reproductive period and by examining in vitro effect of estradiol on Mϕ from young and middle-aged female AO rats. The results showed that: 1) the ability of Mϕ from AO females to “control” the resolution of acute inflammation changes during the early phase of reproductive aging, and these changes are strain-specific (Mϕ from middle-aged AO females that “age more successful” than Dark Agouti females, show properties which may be associated with better "control" of inflammation); 2) these changes are sex-specific (Mϕ from middle-aged females have a greater capacity to “control” inflammation than Mϕ from males of the same age group) and 3) both estradiol and progesterone play important roles in the ability of Mϕ from AO females to “control” acute inflammation. In vitro studies revealed that, in addition to changes in estradiol concentration, intrinsic changes in Mϕ that regulate their response to estradiol action are important for agedependent changes in Mϕ ability to „control“ inflammation.",
publisher = "Univerzitet u Beogradu, Farmaceutski fakultet",
journal = "Univerzitet u Beogradu",
title = "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju",
url = "https://hdl.handle.net/21.15107/rcub_intor_619"
}

Ćuruvija, I. D.. (2021). Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Univerzitet u Beogradu
Univerzitet u Beogradu, Farmaceutski fakultet..
https://hdl.handle.net/21.15107/rcub_intor_619

Ćuruvija ID. Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju. in Univerzitet u Beogradu. 2021;.
https://hdl.handle.net/21.15107/rcub_intor_619 .

Ćuruvija, Ivana D., "Polne i sojne specifičnosti promena citokinskog profila makrofaga ženki pacova u reproduktivnom starenju" in Univerzitet u Beogradu (2021),
https://hdl.handle.net/21.15107/rcub_intor_619 .

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 .

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 .

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 . .

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 . .

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 . .

TY  - JOUR
AU  - Ćuruvija, Ivana
AU  - Stanojević, Stanislava
AU  - Arsenović-Ranin, Nevena
AU  - Blagojević, Veljko
AU  - Dimitrijević, Mirjana
AU  - Vidić-Danković, Biljana
AU  - Vujić, Vesna
PY  - 2017
UR  - http://intor.torlakinstitut.com/handle/123456789/496
AB  - The aim of this study was to examine the influence of sex on age-related changes in phenotype and functional capacity of rat macrophages. The potential role of estradiol as a contributing factor to a sex difference in macrophage function with age was also examined. Thioglycollate-elicited peritoneal macrophages derived from the young (2 months old) and the naturally senescent intact middle-aged (16 months old) male and female rats were tested for cytokine secretion and antimicrobial activity (NO and H2O2 production and myeloperoxidase activity). Serum concentration of estradiol and the expression of estrogen receptor (ER)alpha and ER beta on freshly isolated peritoneal macrophages were also examined. Decreased secretion of IL-1 beta and IL-6 by macrophages from middle-aged compared to the young females was accompanied with the lesser density of macrophage ER alpha expression and the lower systemic level of estradiol, whereas the opposite was true for middle-aged male rats. Macrophages in the middle-aged females, even with the diminished circulating estradiol levels, produce increased amount of IL-6, and comparable amounts of IL-1 beta, TNF-alpha, and NO to that measured in macrophages from the middle-aged males. Age-related changes in macrophage phenotype and the antimicrobial activity were independent of macrophage ER alpha/ER beta expression and estradiol level in both male and female rats. Although our study suggests that the sex difference in the level of circulating estradiol may to some extent contribute to sex difference in macrophage function of middle-aged rats, it also points to more complex hormonal regulation of peritoneal macrophage activity in females.
PB  - Springer/Plenum Publishers, New York
T2  - Inflammation
T1  - Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression
EP  - 1101
IS  - 3
SP  - 1087
VL  - 40
DO  - 10.1007/s10753-017-0551-3
ER  - 

@article{
author = "Ćuruvija, Ivana and Stanojević, Stanislava and Arsenović-Ranin, Nevena and Blagojević, Veljko and Dimitrijević, Mirjana and Vidić-Danković, Biljana and Vujić, Vesna",
year = "2017",
abstract = "The aim of this study was to examine the influence of sex on age-related changes in phenotype and functional capacity of rat macrophages. The potential role of estradiol as a contributing factor to a sex difference in macrophage function with age was also examined. Thioglycollate-elicited peritoneal macrophages derived from the young (2 months old) and the naturally senescent intact middle-aged (16 months old) male and female rats were tested for cytokine secretion and antimicrobial activity (NO and H2O2 production and myeloperoxidase activity). Serum concentration of estradiol and the expression of estrogen receptor (ER)alpha and ER beta on freshly isolated peritoneal macrophages were also examined. Decreased secretion of IL-1 beta and IL-6 by macrophages from middle-aged compared to the young females was accompanied with the lesser density of macrophage ER alpha expression and the lower systemic level of estradiol, whereas the opposite was true for middle-aged male rats. Macrophages in the middle-aged females, even with the diminished circulating estradiol levels, produce increased amount of IL-6, and comparable amounts of IL-1 beta, TNF-alpha, and NO to that measured in macrophages from the middle-aged males. Age-related changes in macrophage phenotype and the antimicrobial activity were independent of macrophage ER alpha/ER beta expression and estradiol level in both male and female rats. Although our study suggests that the sex difference in the level of circulating estradiol may to some extent contribute to sex difference in macrophage function of middle-aged rats, it also points to more complex hormonal regulation of peritoneal macrophage activity in females.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Inflammation",
title = "Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression",
pages = "1101-1087",
number = "3",
volume = "40",
doi = "10.1007/s10753-017-0551-3"
}

Ćuruvija, I., Stanojević, S., Arsenović-Ranin, N., Blagojević, V., Dimitrijević, M., Vidić-Danković, B.,& Vujić, V.. (2017). Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression. in Inflammation
Springer/Plenum Publishers, New York., 40(3), 1087-1101.
https://doi.org/10.1007/s10753-017-0551-3

Ćuruvija I, Stanojević S, Arsenović-Ranin N, Blagojević V, Dimitrijević M, Vidić-Danković B, Vujić V. Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression. in Inflammation. 2017;40(3):1087-1101.
doi:10.1007/s10753-017-0551-3 .

Ćuruvija, Ivana, Stanojević, Stanislava, Arsenović-Ranin, Nevena, Blagojević, Veljko, Dimitrijević, Mirjana, Vidić-Danković, Biljana, Vujić, Vesna, "Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression" in Inflammation, 40, no. 3 (2017):1087-1101,
https://doi.org/10.1007/s10753-017-0551-3 . .

TY  - CONF
AU  - Ćuruvija, Ivana
AU  - Stanislava, Stanojević
AU  - Kovačević-Jovanović, Vesna
AU  - Dimitrijević, Mirjana
AU  - Vujić, Vesna
AU  - Blagojević, Veljko
AU  - Leposavić, Gordana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/670
AB  - smanjena imunološka funkcija kod žena u menopauzi je uglavnom posledica nedostatka hormona ovarijuma u cirkulaciji. Supstituciona hormonska terapija najčešće podrazumeva nadoknadu estrogena, ali ne i progesterona. U ovom radu kao eksperimantalni model izolovane deficijencije progesterona korišćeni su pacovi stari 20 meseci ovarijektomisani na kraju reproduktivnog preioda (starosti 10 meseci) kod kojih je koncentracija estradiola (usled ekstragonadne sinteze) u nivou estradiola kod lažno ovarijektomisanih pacova iste starosti. Ispitivane je intraćelijska ekspresija receptora za estrogene (ER) i progesteron (PR) i sekrecija pro- i anti-inflamatornih citokina i krajnjih produkata metabolizma arginina u slezinskim i peritonealnim makrofagama, u bazalnim uslovima i nakon in vitro stimulacije sa lipopolisaharidom (LPS). Pokazano je da i peritonealne i slezinske makrofage ispoljavaju ER alfa i ER beta, kao i da ovarijektomija ne utiče na ekspresiju ER-a. Većina peritonealnih i slezinskih makrofaga je ispoljavala PR, a ovarijektomija je dovela do povećanja ekspresije PR samo u slezinskim makrofagama. Ovrijektomija je smanjila i sekreciju citokina iz slezinskih (IL-1beta) i peritonealnih makrofaga (TNF-alfa, IL-1beta, IL-10) i povećala sekreciju IL-10 iz slezinskih i TGF-beta iz peritonealnih makrofaga u bazalnim uslovima. Nakon stimulacije LPS-om, slezinske makrofage  ovarijektomisanih pacova su sekretovale manje TNF-alfa i više IL-10, dok su peritonealne makrofage sekretovale manje IL-1beta i TGF-beta nego ćelije istog porekla iz lažno-ovarijektomisanih pacova. Ovarijektomija je smanjila sintezu uree i u slezinskim i u peritonealnim makrofagama stimulisanim LPS-om. Dugotrajna izolovana deficijencija progesterona u post-reproduktivnom periodu narušava ravnotežu u produkciji pro-/anti-inflamatornih citokina slezinskih i peritonealnih makrofaga.
C3  - VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata
T1  - Promene u citokinskom sekretornom profilu makrofaga starih ženki pacova usled nedostatka progesterona u postreproduktivnom periodu
UR  - https://hdl.handle.net/21.15107/rcub_intor_670
ER  - 

@conference{
author = "Ćuruvija, Ivana and Stanislava, Stanojević and Kovačević-Jovanović, Vesna and Dimitrijević, Mirjana and Vujić, Vesna and Blagojević, Veljko and Leposavić, Gordana",
year = "2016",
abstract = "smanjena imunološka funkcija kod žena u menopauzi je uglavnom posledica nedostatka hormona ovarijuma u cirkulaciji. Supstituciona hormonska terapija najčešće podrazumeva nadoknadu estrogena, ali ne i progesterona. U ovom radu kao eksperimantalni model izolovane deficijencije progesterona korišćeni su pacovi stari 20 meseci ovarijektomisani na kraju reproduktivnog preioda (starosti 10 meseci) kod kojih je koncentracija estradiola (usled ekstragonadne sinteze) u nivou estradiola kod lažno ovarijektomisanih pacova iste starosti. Ispitivane je intraćelijska ekspresija receptora za estrogene (ER) i progesteron (PR) i sekrecija pro- i anti-inflamatornih citokina i krajnjih produkata metabolizma arginina u slezinskim i peritonealnim makrofagama, u bazalnim uslovima i nakon in vitro stimulacije sa lipopolisaharidom (LPS). Pokazano je da i peritonealne i slezinske makrofage ispoljavaju ER alfa i ER beta, kao i da ovarijektomija ne utiče na ekspresiju ER-a. Većina peritonealnih i slezinskih makrofaga je ispoljavala PR, a ovarijektomija je dovela do povećanja ekspresije PR samo u slezinskim makrofagama. Ovrijektomija je smanjila i sekreciju citokina iz slezinskih (IL-1beta) i peritonealnih makrofaga (TNF-alfa, IL-1beta, IL-10) i povećala sekreciju IL-10 iz slezinskih i TGF-beta iz peritonealnih makrofaga u bazalnim uslovima. Nakon stimulacije LPS-om, slezinske makrofage  ovarijektomisanih pacova su sekretovale manje TNF-alfa i više IL-10, dok su peritonealne makrofage sekretovale manje IL-1beta i TGF-beta nego ćelije istog porekla iz lažno-ovarijektomisanih pacova. Ovarijektomija je smanjila sintezu uree i u slezinskim i u peritonealnim makrofagama stimulisanim LPS-om. Dugotrajna izolovana deficijencija progesterona u post-reproduktivnom periodu narušava ravnotežu u produkciji pro-/anti-inflamatornih citokina slezinskih i peritonealnih makrofaga.",
journal = "VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata",
title = "Promene u citokinskom sekretornom profilu makrofaga starih ženki pacova usled nedostatka progesterona u postreproduktivnom periodu",
url = "https://hdl.handle.net/21.15107/rcub_intor_670"
}

Ćuruvija, I., Stanislava, S., Kovačević-Jovanović, V., Dimitrijević, M., Vujić, V., Blagojević, V.,& Leposavić, G.. (2016). Promene u citokinskom sekretornom profilu makrofaga starih ženki pacova usled nedostatka progesterona u postreproduktivnom periodu. in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata.
https://hdl.handle.net/21.15107/rcub_intor_670

Ćuruvija I, Stanislava S, Kovačević-Jovanović V, Dimitrijević M, Vujić V, Blagojević V, Leposavić G. Promene u citokinskom sekretornom profilu makrofaga starih ženki pacova usled nedostatka progesterona u postreproduktivnom periodu. in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata. 2016;.
https://hdl.handle.net/21.15107/rcub_intor_670 .

Ćuruvija, Ivana, Stanislava, Stanojević, Kovačević-Jovanović, Vesna, Dimitrijević, Mirjana, Vujić, Vesna, Blagojević, Veljko, Leposavić, Gordana, "Promene u citokinskom sekretornom profilu makrofaga starih ženki pacova usled nedostatka progesterona u postreproduktivnom periodu" in VII Naučni sastanak Društva imunologa Srbije, Program i knjiga apstrakata (2016),
https://hdl.handle.net/21.15107/rcub_intor_670 .

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 .

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 . .

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Petrović, Raisa
AU  - Vujić, Vesna
AU  - Dimitrijević, Mirjana
PY  - 2016
UR  - http://intor.torlakinstitut.com/handle/123456789/453
AB  - Rats of Albino Oxford (AO) strain in our animal facility exhibit a longer average healthy life span than rats of Dark Agouit (DA) strain. Since chronic activation of macrophages contributes to chronic low level inflammation common in older age, elucidation of the changes in middle-aged rats could be useful in prevention of unbalanced inflammatory response in advanced age. We have analysed the phenotype of unelicited and thioglycollate-elicited peritoneal macrophages from young and middle-aged DA and AO rats and tested functions of these cells following stimulation with lipopolysaccharide (LPS) in vitro. Unelicited cells from middle-aged DA rats produced higher amounts of proinflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO), but have a diminished response to LPS stimulation then cells from young rats, in spite of increased frequency of TLR4- and CD14-expressing mature macrophages. Injection of thioglycollate robustly increased overall cytokine production in young rats' macrophages, while diminishing their response to LPS stimulation. In middle-aged DA rats injection of thioglycollate diminished IL-6 production, but increased it in response to LPS stimulation. Quite the contrary to DA rats, the macrophages from middle-aged AO rats have released diminished levels of TNF-alpha, and NO, whereas urea production was strongly increased, when compared to the macrophages from young rats. Although the thioglycollate injection has increased the proportion of CD86(+)MHCII(+) mature macrophages in young rats, and percentages of activated TLR4(+) macrophages in both age groups of AO rats, it has not affected the cytokine production in young rats' macrophages, and the TNF-alpha production in middle-aged rats' macrophages. Moreover, the injection of thioglycollate has robustly increased the production of urea in macrophages derived from both age groups of AO rats. Although middle-aged rats of both strains were healthy during experiment, differences between the inflammatory responses of peritoneal macrophages of middle-aged rats of these strains might be one of the contributing factors defining their health in their advanced age. Development of strategies for the prevention of undesirable inflammatory changes in the elderly would benefit from the prospective study of the middle-aged. (C) 2016 Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging
EP  - 107
SP  - 95
VL  - 85
DO  - 10.1016/j.exger.2016.10.005
ER  - 

@article{
author = "Stanojević, Stanislava and Ćuruvija, Ivana and Blagojević, Veljko and Petrović, Raisa and Vujić, Vesna and Dimitrijević, Mirjana",
year = "2016",
abstract = "Rats of Albino Oxford (AO) strain in our animal facility exhibit a longer average healthy life span than rats of Dark Agouit (DA) strain. Since chronic activation of macrophages contributes to chronic low level inflammation common in older age, elucidation of the changes in middle-aged rats could be useful in prevention of unbalanced inflammatory response in advanced age. We have analysed the phenotype of unelicited and thioglycollate-elicited peritoneal macrophages from young and middle-aged DA and AO rats and tested functions of these cells following stimulation with lipopolysaccharide (LPS) in vitro. Unelicited cells from middle-aged DA rats produced higher amounts of proinflammatory mediators interleukin-6 (IL-6) and nitric oxide (NO), but have a diminished response to LPS stimulation then cells from young rats, in spite of increased frequency of TLR4- and CD14-expressing mature macrophages. Injection of thioglycollate robustly increased overall cytokine production in young rats' macrophages, while diminishing their response to LPS stimulation. In middle-aged DA rats injection of thioglycollate diminished IL-6 production, but increased it in response to LPS stimulation. Quite the contrary to DA rats, the macrophages from middle-aged AO rats have released diminished levels of TNF-alpha, and NO, whereas urea production was strongly increased, when compared to the macrophages from young rats. Although the thioglycollate injection has increased the proportion of CD86(+)MHCII(+) mature macrophages in young rats, and percentages of activated TLR4(+) macrophages in both age groups of AO rats, it has not affected the cytokine production in young rats' macrophages, and the TNF-alpha production in middle-aged rats' macrophages. Moreover, the injection of thioglycollate has robustly increased the production of urea in macrophages derived from both age groups of AO rats. Although middle-aged rats of both strains were healthy during experiment, differences between the inflammatory responses of peritoneal macrophages of middle-aged rats of these strains might be one of the contributing factors defining their health in their advanced age. Development of strategies for the prevention of undesirable inflammatory changes in the elderly would benefit from the prospective study of the middle-aged. (C) 2016 Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging",
pages = "107-95",
volume = "85",
doi = "10.1016/j.exger.2016.10.005"
}

Stanojević, S., Ćuruvija, I., Blagojević, V., Petrović, R., Vujić, V.,& Dimitrijević, M.. (2016). Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 85, 95-107.
https://doi.org/10.1016/j.exger.2016.10.005

Stanojević S, Ćuruvija I, Blagojević V, Petrović R, Vujić V, Dimitrijević M. Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging. in Experimental Gerontology. 2016;85:95-107.
doi:10.1016/j.exger.2016.10.005 .

Stanojević, Stanislava, Ćuruvija, Ivana, Blagojević, Veljko, Petrović, Raisa, Vujić, Vesna, Dimitrijević, Mirjana, "Strain-dependent response to stimulation in middle-aged rat macrophages: A quest after a useful indicator of healthy aging" in Experimental Gerontology, 85 (2016):95-107,
https://doi.org/10.1016/j.exger.2016.10.005 . .

TY  - CONF
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Petrović, Raisa
AU  - Vujnović, I.
AU  - Dimitrijević, Mirjana
AU  - Vujić, V.
AU  - Stanojević, Stanislava
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/671
AB  - The influence of aging on phagocytic, antigen presenting and secretory capacity of resident Albino Oxford rat peritoneal macrophages cultured for 24 hours in medium alone and in the presence of either LPS or IL-4 was examined. The frequencies of CD68+, CD169+ and CCR7+ cells were comparable among fresh peritoneal cells from young (3-months-old) and aged (i8-months-old) rats, whereas those of CD163+, MHCII+ and CD86+ cells were lower within the same cell population in aged relative to young rats. Congruent with the latter findings, aged rat macrophages cultured in medium alone exhibited impaired allostimulatory properties. Additionally, their zymosan phagocytizing ability was reduced. Differently from young rat macrophages, aged rat macrophages changed neither allostimulatory nor zymosan phagocytizing ability upon in vitro treatment with either LPS or IL-4. In the presence of LPS, NO production comparably increased in macrophages from young and aged rats. However, in the presence of either LPS or IL-4 urea production increased only in macrophages from aged rats. Differently from LPS, which increased the prototypic proinflamrnatory cytokine production in macrophages from rats of both ages, the diminishing effect of IL-4 on their production was evident only in macrophages from young rats. Collectively, our results suggest that aging, besides diminishing influence on macrophage allostimulatory and zymosan phagocytizing ability, may impair their responsiveness to IL-4 in vitro. Consequently, an altered efficacy of inflammatory/immune responses in aged rats may be expected.
C3  - 4th European Congress of Immunology, Vienna 2015, September 6-9, abstract book
T1  - Aged rat macrophages exhibit ipaired response to in vitro stimulation with IL-4
EP  - 341
SP  - 341
SP  - P.C.12.06
UR  - https://hdl.handle.net/21.15107/rcub_intor_671
ER  - 

@conference{
author = "Blagojević, Veljko and Ćuruvija, Ivana and Petrović, Raisa and Vujnović, I. and Dimitrijević, Mirjana and Vujić, V. and Stanojević, Stanislava and Leposavić, Gordana",
year = "2015",
abstract = "The influence of aging on phagocytic, antigen presenting and secretory capacity of resident Albino Oxford rat peritoneal macrophages cultured for 24 hours in medium alone and in the presence of either LPS or IL-4 was examined. The frequencies of CD68+, CD169+ and CCR7+ cells were comparable among fresh peritoneal cells from young (3-months-old) and aged (i8-months-old) rats, whereas those of CD163+, MHCII+ and CD86+ cells were lower within the same cell population in aged relative to young rats. Congruent with the latter findings, aged rat macrophages cultured in medium alone exhibited impaired allostimulatory properties. Additionally, their zymosan phagocytizing ability was reduced. Differently from young rat macrophages, aged rat macrophages changed neither allostimulatory nor zymosan phagocytizing ability upon in vitro treatment with either LPS or IL-4. In the presence of LPS, NO production comparably increased in macrophages from young and aged rats. However, in the presence of either LPS or IL-4 urea production increased only in macrophages from aged rats. Differently from LPS, which increased the prototypic proinflamrnatory cytokine production in macrophages from rats of both ages, the diminishing effect of IL-4 on their production was evident only in macrophages from young rats. Collectively, our results suggest that aging, besides diminishing influence on macrophage allostimulatory and zymosan phagocytizing ability, may impair their responsiveness to IL-4 in vitro. Consequently, an altered efficacy of inflammatory/immune responses in aged rats may be expected.",
journal = "4th European Congress of Immunology, Vienna 2015, September 6-9, abstract book",
title = "Aged rat macrophages exhibit ipaired response to in vitro stimulation with IL-4",
pages = "341-341-P.C.12.06",
url = "https://hdl.handle.net/21.15107/rcub_intor_671"
}

Blagojević, V., Ćuruvija, I., Petrović, R., Vujnović, I., Dimitrijević, M., Vujić, V., Stanojević, S.,& Leposavić, G.. (2015). Aged rat macrophages exhibit ipaired response to in vitro stimulation with IL-4. in 4th European Congress of Immunology, Vienna 2015, September 6-9, abstract book, 341-341.
https://hdl.handle.net/21.15107/rcub_intor_671

Blagojević V, Ćuruvija I, Petrović R, Vujnović I, Dimitrijević M, Vujić V, Stanojević S, Leposavić G. Aged rat macrophages exhibit ipaired response to in vitro stimulation with IL-4. in 4th European Congress of Immunology, Vienna 2015, September 6-9, abstract book. 2015;:341-341.
https://hdl.handle.net/21.15107/rcub_intor_671 .

Blagojević, Veljko, Ćuruvija, Ivana, Petrović, Raisa, Vujnović, I., Dimitrijević, Mirjana, Vujić, V., Stanojević, Stanislava, Leposavić, Gordana, "Aged rat macrophages exhibit ipaired response to in vitro stimulation with IL-4" in 4th European Congress of Immunology, Vienna 2015, September 6-9, abstract book (2015):341-341,
https://hdl.handle.net/21.15107/rcub_intor_671 .

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 .

TY  - JOUR
AU  - Stanojević, Stanislava
AU  - Kovačević-Jovanović, Vesna
AU  - Dimitrijević, Mirjana
AU  - Vujić, Vesna
AU  - Ćuruvija, Ivana
AU  - Blagojević, Veljko
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/423
AB  - Problem The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied. Method of study Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro. Results Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1 beta) and peritoneal (TNF-alpha, IL-1 beta, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-beta by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-alpha and more IL-10, whereas peritoneal macrophages produced less IL-1 beta and TGF-beta than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages. Conclusion Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro- inflammatory/anti-inflammatory cytokine secretory balance.
PB  - Wiley, Hoboken
T2  - American Journal of Reproductive Immunology
T1  - Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat
EP  - 456
IS  - 5
SP  - 445
VL  - 74
DO  - 10.1111/aji.12424
ER  - 

@article{
author = "Stanojević, Stanislava and Kovačević-Jovanović, Vesna and Dimitrijević, Mirjana and Vujić, Vesna and Ćuruvija, Ivana and Blagojević, Veljko and Leposavić, Gordana",
year = "2015",
abstract = "Problem The influence of unopposed estrogen replacement/isolated progesterone deficiency on macrophage production of pro-inflammatory/anti-inflammatory mediators in the post-reproductive age was studied. Method of study Considering that in the rats post-ovariectomy the circulating estradiol, but not progesterone level rises to the values in sham-operated controls, 20-month-old rats ovariectomized at the age of 10 months served as an experimental model. Estrogen and progesterone receptor expression, secretion of pro- and anti-inflammatory cytokines, and arginine metabolism end-products were examined in splenic and peritoneal macrophages under basal conditions and following lipopolysaccharide (LPS) stimulation in vitro. Results Almost all peritoneal and a subset of splenic macrophages expressed the intracellular progesterone receptor. Ovariectomy diminished cytokine production by splenic (IL-1 beta) and peritoneal (TNF-alpha, IL-1 beta, IL-10) macrophages and increased the production of IL-10 by splenic and TGF-beta by peritoneal cells under basal conditions. Following LPS stimulation, splenic macrophages from ovariectomized rats produced less TNF-alpha and more IL-10, whereas peritoneal macrophages produced less IL-1 beta and TGF-beta than the corresponding cells from sham-operated rats. Ovariectomy diminished urea production in both subpopulations of LPS-stimulated macrophages. Conclusion Although long-lasting isolated progesterone deficiency in the post-reproductive age differentially affects cytokine production in the macrophages from distinct tissue compartments, in both subpopulations, it impairs the pro- inflammatory/anti-inflammatory cytokine secretory balance.",
publisher = "Wiley, Hoboken",
journal = "American Journal of Reproductive Immunology",
title = "Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat",
pages = "456-445",
number = "5",
volume = "74",
doi = "10.1111/aji.12424"
}

Stanojević, S., Kovačević-Jovanović, V., Dimitrijević, M., Vujić, V., Ćuruvija, I., Blagojević, V.,& Leposavić, G.. (2015). Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat. in American Journal of Reproductive Immunology
Wiley, Hoboken., 74(5), 445-456.
https://doi.org/10.1111/aji.12424

Stanojević S, Kovačević-Jovanović V, Dimitrijević M, Vujić V, Ćuruvija I, Blagojević V, Leposavić G. Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat. in American Journal of Reproductive Immunology. 2015;74(5):445-456.
doi:10.1111/aji.12424 .

Stanojević, Stanislava, Kovačević-Jovanović, Vesna, Dimitrijević, Mirjana, Vujić, Vesna, Ćuruvija, Ivana, Blagojević, Veljko, Leposavić, Gordana, "Unopposed Estrogen Supplementation/Progesterone Deficiency in Post-Reproductive Age Affects the Secretory Profile of Resident Macrophages in a Tissue-Specific Manner in the Rat" in American Journal of Reproductive Immunology, 74, no. 5 (2015):445-456,
https://doi.org/10.1111/aji.12424 . .