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Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains

Authorized Users Only
2014
Authors
Dimitrijević, Mirjana
Stanojević, Stanislava
Vujić, Vesna
Aleksić, Iva
Pilipović, Ivan
Leposavić, Gordana
Article (Published version)
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Abstract
Altered functions of macrophages with aging contribute to impairment of both innate and adaptive immunity in the elderly. The present study aimed to examine strain specificity of age-related changes in the phenotypic and functional characteristics of macrophages from DA and AO rats, which differ in average life span. Resident peritoneal macrophages from young (10-12 weeks old) and aged (98-104 weeks old) rats were tested for: (a) the surface expression of TLR4 and CD14; (b) the basal and LPS-induced production of TNF-alpha and IL-10; and (c) the basal and LPS-induced activity of iNOS and arginase, by measuring the levels of NO and urea, respectively, in the culture supernatants. Aging elevated TLR4 macrophage surface density in rats of both strains. Conversely, the age-related decrease in the surface density of CD14 co-receptor was detected only on macrophages from aged DA rats. Accordingly, with aging in DA rats, contrary to AO rats, upon LPS-stimulation both TNF-alpha and IL-10 level...s decreased in culture supernatants. However, in rats of both strains TNF-alpha stimulation index (LPS-induced over basal production) remained stable with aging, but it was significantly greater in AO rats. Furthermore, with aging, IL-10 stimulation index decreased and increased in DA and AO rats, respectively. Age-related shift in urea stimulation index complied with the changes of IL-10 stimulation index during aging. In conclusion, the study suggests that the preserved ability of macrophages from aged AO rats to synthesize not only proinflammatory TNF-alpha, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats.

Keywords:
Aging / Macrophages / Cytokines / NO/urea balance / DP4 / Rat strains
Source:
Biogerontology, 2014, 15, 5, 475-486
Publisher:
  • Springer, New York
Funding / projects:
  • Immune system plasticity during aging: Immunomodulatory capacity of oestrogens (RS-175050)

DOI: 10.1007/s10522-014-9513-4

ISSN: 1389-5729

PubMed: 25009084

WoS: 000342080300006

Scopus: 2-s2.0-84906936202
[ Google Scholar ]
18
17
URI
http://intor.torlakinstitut.com/handle/123456789/402
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Torlak
TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Stanojević, Stanislava
AU  - Vujić, Vesna
AU  - Aleksić, Iva
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/402
AB  - Altered functions of macrophages with aging contribute to impairment of both innate and adaptive immunity in the elderly. The present study aimed to examine strain specificity of age-related changes in the phenotypic and functional characteristics of macrophages from DA and AO rats, which differ in average life span. Resident peritoneal macrophages from young (10-12 weeks old) and aged (98-104 weeks old) rats were tested for: (a) the surface expression of TLR4 and CD14; (b) the basal and LPS-induced production of TNF-alpha and IL-10; and (c) the basal and LPS-induced activity of iNOS and arginase, by measuring the levels of NO and urea, respectively, in the culture supernatants. Aging elevated TLR4 macrophage surface density in rats of both strains. Conversely, the age-related decrease in the surface density of CD14 co-receptor was detected only on macrophages from aged DA rats. Accordingly, with aging in DA rats, contrary to AO rats, upon LPS-stimulation both TNF-alpha and IL-10 levels decreased in culture supernatants. However, in rats of both strains TNF-alpha stimulation index (LPS-induced over basal production) remained stable with aging, but it was significantly greater in AO rats. Furthermore, with aging, IL-10 stimulation index decreased and increased in DA and AO rats, respectively. Age-related shift in urea stimulation index complied with the changes of IL-10 stimulation index during aging. In conclusion, the study suggests that the preserved ability of macrophages from aged AO rats to synthesize not only proinflammatory TNF-alpha, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats.
PB  - Springer, New York
T2  - Biogerontology
T1  - Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains
EP  - 486
IS  - 5
SP  - 475
VL  - 15
DO  - 10.1007/s10522-014-9513-4
UR  - conv_340
ER  - 
@article{
author = "Dimitrijević, Mirjana and Stanojević, Stanislava and Vujić, Vesna and Aleksić, Iva and Pilipović, Ivan and Leposavić, Gordana",
year = "2014",
abstract = "Altered functions of macrophages with aging contribute to impairment of both innate and adaptive immunity in the elderly. The present study aimed to examine strain specificity of age-related changes in the phenotypic and functional characteristics of macrophages from DA and AO rats, which differ in average life span. Resident peritoneal macrophages from young (10-12 weeks old) and aged (98-104 weeks old) rats were tested for: (a) the surface expression of TLR4 and CD14; (b) the basal and LPS-induced production of TNF-alpha and IL-10; and (c) the basal and LPS-induced activity of iNOS and arginase, by measuring the levels of NO and urea, respectively, in the culture supernatants. Aging elevated TLR4 macrophage surface density in rats of both strains. Conversely, the age-related decrease in the surface density of CD14 co-receptor was detected only on macrophages from aged DA rats. Accordingly, with aging in DA rats, contrary to AO rats, upon LPS-stimulation both TNF-alpha and IL-10 levels decreased in culture supernatants. However, in rats of both strains TNF-alpha stimulation index (LPS-induced over basal production) remained stable with aging, but it was significantly greater in AO rats. Furthermore, with aging, IL-10 stimulation index decreased and increased in DA and AO rats, respectively. Age-related shift in urea stimulation index complied with the changes of IL-10 stimulation index during aging. In conclusion, the study suggests that the preserved ability of macrophages from aged AO rats to synthesize not only proinflammatory TNF-alpha, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains",
pages = "486-475",
number = "5",
volume = "15",
doi = "10.1007/s10522-014-9513-4",
url = "conv_340"
}
Dimitrijević, M., Stanojević, S., Vujić, V., Aleksić, I., Pilipović, I.,& Leposavić, G.. (2014). Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains. in Biogerontology
Springer, New York., 15(5), 475-486.
https://doi.org/10.1007/s10522-014-9513-4
conv_340
Dimitrijević M, Stanojević S, Vujić V, Aleksić I, Pilipović I, Leposavić G. Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains. in Biogerontology. 2014;15(5):475-486.
doi:10.1007/s10522-014-9513-4
conv_340 .
Dimitrijević, Mirjana, Stanojević, Stanislava, Vujić, Vesna, Aleksić, Iva, Pilipović, Ivan, Leposavić, Gordana, "Aging oppositely affects TNF-alpha and IL-10 production by macrophages from different rat strains" in Biogerontology, 15, no. 5 (2014):475-486,
https://doi.org/10.1007/s10522-014-9513-4 .,
conv_340 .

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