期刊
NEUROIMMUNOMODULATION
卷 9, 期 4, 页码 183-192出版社
KARGER
DOI: 10.1159/000049025
关键词
aging; brain; cytokines; interleukin-6; interleukin-10
资金
- NIA NIH HHS [AG16710] Funding Source: Medline
- NIDDK NIH HHS [DK51576] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R29DK051576] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG016710] Funding Source: NIH RePORTER
Objectives: The DNA-binding activity of nuclear factor kappaB (NFkappaB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6. Methods: In initial studies coronal brain sections and filial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipopolysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFkappaB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined. Results: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFkappaB to the IL-6 gene promoter. The decrease in NFkappaB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFkappaB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion. Conclusions: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene. Copyright (C) 2002 S. Karger AG, Basel.
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