Regulation of levels of IL-1 mRNA in human fibroblasts

✍ Scribed by Kenji Yamato; Ziad El-Hajjaoui; H. Phillip Koeffler

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 913 KB
• Volume: 139
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041390322

✦ Synopsis

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 (TNFa) and activators of protein kinase C including 12-0-tetradecanoylphorbol-13-acetate (TPA) and teleocidin induced the accumulation of IL-l p mRNA in human fibroblasts (WI-38). Effect of TNFa was not blocked by inhibitors of either protein synthesis (cycloheximide) or protein kinase C activity. Accumulation of IL-l p mRNA was also increased by a calcium ionophore (A23187) and an inhibitor of the N a f / K f pump (ouabain); both compounds are known to increase cytoplasmic levels of C a + + . Stability of I L -l P mRNA in fibroblasts exposed to TPA was more than fourfold greater than after fibroblasts were exposed to either TNFa or cycloheximide. This suggests that posttranscriptional stabilization of IL-1 p mRNA is a major mechanism leading to accumulation of IL-10 mRNA after activation of PKC in fibroblasts. Fibroblasts did not express I L -l a mRNA after exposure to stimuli which induced the accumulation of IL-1 p mRNA. In summary, several different pathways regulate levels of IL-1 p mRNA in human mesenchymal cells.