Regulation of levels of IL-1 mRNA in human fibroblasts.
Interleukin-1 (IL-1) has a crucial role in host defenses, inflammatory processes, and tissue homeostasis. A wide variety of cells produce this protein in response to a number of extracellular stimuli including microorganisms, antigenic stimuli, and products from other cells. Regulation of IL-1 production at the molecular level is poorly understood. We studied expression, intracellular signals, and posttranscriptional regulation of IL-1 mRNA in human mesenchymal cells by using Northern blot analysis. Tumor necrosis factor alpha (TNF alpha) and activators of protein kinase C including 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin induced the accumulation of IL-1 beta mRNA in human fibroblasts (WI-38). Effect of TNF alpha was not blocked by inhibitors of either protein synthesis (cycloheximide) or protein kinase C activity. Accumulation of IL-1 beta mRNA was also increased by a calcium ionophore (A23187) and an inhibitor of the Na+/K+ pump (ouabain); both compounds are known to increase cytoplasmic levels of Ca++. Stability of IL-1 beta mRNA in fibroblasts exposed to TPA was more than fourfold greater than after fibroblasts were exposed to either TNF alpha or cycloheximide. This suggests that posttranscriptional stabilization of IL-1 beta mRNA is a major mechanism leading to accumulation of IL-1 beta mRNA after activation of PKC in fibroblasts. Fibroblasts did not express IL-1 alpha mRNA after exposure to stimuli which induced the accumulation of IL-1 beta mRNA. In summary, several different pathways regulate levels of IL-1 beta mRNA in human mesenchymal cells.
Yamato
K
K
Department of Medicine, UCLA School of Medicine 90024.
el-Hajjaoui
Z
Z
Koeffler
H P
HP
D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D010042:Ouabain; D003513:Cycloheximide; D008715:Methionine; D013755:Tetradecanoylphorbol Acetate