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

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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-α 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-α and IL-10 levels decreased in culture supernatants. However, in rats of both strains TNF-α 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-α, but also immunoregulatory IL-10 cytokine most likely contributes to their longer average life compared with DA rats.

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Acknowledgments

This study was supported by Grant No. 175050 from Ministry of Education, Science and Technology of Republic of Serbia.

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Authors and Affiliations

  1. Institute of Virology, Vaccines and Sera, “Torlak”, Immunology Research Center “Branislav Janković”, Vojvode Stepe 458, 11152, Belgrade, Serbia

    Mirjana Dimitrijević, Stanislava Stanojević, Iva Aleksić & Ivan Pilipović

  2. Institute of Chemistry in Medicine, School of Medicine, University of Belgrade, Belgrade, Serbia, Višegradska 26, 11000, Belgrade, Serbia

    Vesna Vujić

  3. Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia, Vojvode Stepe 450, 11221, Belgrade, Serbia

    Gordana Leposavić

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  1. Mirjana Dimitrijević
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  2. Stanislava Stanojević
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  3. Vesna Vujić
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  4. Iva Aleksić
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  5. Ivan Pilipović
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  6. Gordana Leposavić
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Correspondence to Mirjana Dimitrijević.

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Dimitrijević, M., Stanojević, S., Vujić, V. et al. Aging oppositely affects TNF-α and IL-10 production by macrophages from different rat strains. Biogerontology 15, 475–486 (2014). https://doi.org/10.1007/s10522-014-9513-4

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  • DOI: https://doi.org/10.1007/s10522-014-9513-4

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