Protein kinase C modulates the amounts of IL-1 receptor mRNA in human lung fibroblasts

T. R. Aksamit, M. M. Monick, G. W. Hunninghake

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

IL-1 activates human lung fibroblasts via IL-1-specific membrane receptors. The numbers of IL-1 binding sites on fibroblasts are increased after exposure to prostaglandin E2 (PGE2) or IL-1. Increases in binding sites are associated with changes in functional responses to IL-1. In these studies, we determined if alterations in numbers of IL-1 binding sites on human lung fibroblasts were associated with parallel changes in IL-1R mRNA. In addition, since IL-1 and PGE2 can activate protein kinase C (PKC) and protein kinase A (PKA), we exposed human lung fibroblasts to 1-(5- Isoquinoline sulfonyl)-2-methylpiperafine (H7) or staurosporine, which are relatively specific inhibitors of PKC, and N-[2-(methylamino)ethyl]-5- isoquinolinesulfomamide (H8), an inhibitor of PKA, to determine whether the IL-1 and PGE2 stimulated increases in binding sites were mediated by activation of PKC or PKA. H7 decreased the base line and PGE2-stimulated increases in numbers of IL-1 binding sites. Exposure of the fibroblasts to phorbol-12-myristate-13-acetate (PMA) for 24 h, which is known to deplete PKC, also decreased the numbers of base line IL-1 binding sites. These changes were paralleled by changes in amounts of IL-1R mRNA. H7 and staurosporine also blocked IL-1 and PGE2 stimulated increases in IL-1R mRNA. In contrast, H8 had no effect on the base line or PGE2-stimulated increases in numbers of IL-1 binding sites nor did it change the amounts of IL-1R mRNA. These studies show that changes in the numbers of IL-1 binding sites on human lung fibroblasts are paralleled by changes in IL-1R mRNA. In addition, PKC activity is necessary for the expression of both base line and stimulated increases in IL-1 binding sites and IL-1R mRNA. These studies suggest that PKC activity plays an important role in the modulation of IL-1R expression.

Original languageEnglish (US)
Pages (from-to)284-290
Number of pages7
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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