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

被引:22
|
作者
Dimitrijevic, Mirjana [1 ]
Stanojevic, Stanislava [1 ]
Vujic, Vesna [2 ]
Aleksic, Iva [1 ]
Pilipovic, Ivan [1 ]
Leposavic, Gordana [3 ]
机构
[1] Immunol Res Ctr Branislav Jankovic, Inst Virol Vaccines & Sera, Belgrade 11152, Serbia
[2] Univ Belgrade, Sch Med, Inst Med Chem, Belgrade 11000, Serbia
[3] Univ Belgrade, Dept Physiol, Fac Pharm, Belgrade 11221, Serbia
关键词
Aging; Macrophages; Cytokines; NO/urea balance; DP4; Rat strains; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DIPEPTIDYL-PEPTIDASE-IV; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; CYTOKINE PRODUCTION; ADJUVANT ARTHRITIS; PERITONEAL-MACROPHAGES; ALBINO OXFORD; ARGINASE-I; F344; RATS;
D O I
10.1007/s10522-014-9513-4
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:475 / 486
页数:12
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