An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice.
OBJECTIVE
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 glial 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.
Ye
S M
SM
Laboratory of Integrative Biology, Department of Animal Sciences, University of Illinois, Urbana, IL 61801, USA.
Johnson
R W
RW
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D001923:Brain Chemistry; D018507:Gene Expression Regulation, Developmental; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10