Role of protein kinase C activation in synthesis of complement components C2 and factor B in interferon-γ-stimulated human fibroblasts, glioblastoma cell line A172 and monocytes

I. Watanabe, T. Horiuchi, S. Fujita

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10 Citations (Scopus)

Abstract

The synthesis of C2 and factor B, the key components of complement system, is performed by various kinds of cells and is also up-regulated by interferon-γ (IFN-γ). By using human fibroblasts, human glioblastoma cell line A172 and monocytes, we investigated the signal-transduction mechanism for IFN-γ-induced synthesis of C2 and factor B. The C2 and factor B synthesis induced by IFN-γ in all three cell types was inhibited by a protein kinase C (PKC) inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7). The depletion of PKC in these cell types after treatment with phorbol 12-myristate 13-acetate (PMA) resulted in inhibition of IFN-γ-induced C2 production. In addition, IFN-γ treatment elicited a decrease in cytoplasmic PKC in A172 cells, indicating that PKC is activated by IFN-γ. These results suggest that PKC is crucial for IFN-γ-induced C2 and factor B synthesis. Northern-blot analysis showed that the effects at H-7 were at least partly mediated by modulation of C2 and factor B mRNA abundance in A172 cells. Since treatment of fibroblasts and A172 cells with IFN-γ had no effect on intracellular Ca2+ concentration, and since neither EGTA nor nifedipine inhibited C2 or factor B synthesis induced by IFN-γ, we concluded that intracellular Ca2+ mobilization was not involved in the effect of IFN-γ. In addition, genistein, herbimycin A and N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) had no inhibitory effect on IFN-γ-mediated action in any of the three cell types, which suggests that IFN-γ acts independently of tyrosine kinases and calmodulin-dependent protein kinases.

Original languageEnglish
Pages (from-to)425-431
Number of pages7
JournalBiochemical Journal
Volume305
Issue number2
DOIs
Publication statusPublished - 1995

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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