Basal and induced amounts of interleukin-6 mRNA decline progressively with age in human fibroblasts.
Interleukin-6 (IL-6) is a multi-functional cytokine that plays a role in the body's response to injury and infection. IL-6 expression is induced in young human diploid fibroblasts (HDF) in response to a number of agents including fetal bovine serum, 12-O-tetradecanoylphorbol-13-acetate, double-stranded RNA, and forskolin. In contrast, we find that senescent HDF are markedly deficient in their ability to express IL-6 in response to serum, double-stranded RNA, and 12-O-tetradecanoyl-phorbol-13-acetate, whereas forskolin is still an effective inducer for senescent cells. Thus, specific pathways for stimulating IL-6 expression appear to be blocked in senescent HDF. The basal amount of IL-6 mRNA in unstimulated senescent HDF is also much lower than in unstimulated young quiescent HDF. Likewise, the amount of IL-6 protein produced by senescent HDF is decreased at least 10-fold. Both the basal and induced levels of IL-6 declined progressively with aging of the HDF in culture, e.g. IL-6 cannot be induced above the young basal level by approximately 65% of life-span completed. If a similar decrease in IL-6 expression takes place in HDF in vivo, it could contribute to the decline in wound healing and the increase in the number and severity of infections experienced by aged individuals.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347.
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D001769:Blood / Q000378:metabolism; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004171:Diploidy; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D015850:Interleukin-6; D012333:RNA, Messenger; D005576:Colforsin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate