Protein kinase C inhibitors block the activation of macrophages by IFN-β but not by IFN-γ

D. Radzioch, L. Varesio

Research output: Contribution to journalArticle

Abstract

We investigated the role of protein kinase C (PK-C) in the activation of cytotoxic peritoneal murine macrophages (MΦ) by IFN-γ or by IFN-β. Two potent inhibitors of PK-C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and retinal, were used. We found that both drugs inhibited in a dose-dependent manner the activation of cytotoxicity induced by IFN-β, suggesting the requirement for intact PK-C activity in this process. In contrast, neither H-7 nor retinal inhibited the activation of cytotoxic MΦ by IFN-γ, indicating that IFN-γ acts through a PK-C-independent pathway. The effectiveness of both drugs in inhibiting PK-C in intact MΦ was evaluated by measuring the inhibition of induction of c-fos mRNA by L-α-1-oleoyl-2-acetoyl-sn-3-glycerol, a process that has been shown to be dependent on PK-C activation. We have found a strict correlation in the dose-dependent inhibition by both drugs of c-fos mRNA induction and activation of MΦ by IFN-β. These results indicate that different pathways of activation are triggered by IFN-γ and IFN-β, the former being independent from and the latter dependent on intact PK-C activity.

Original languageEnglish
Pages (from-to)1259-1263
Number of pages5
JournalJournal of Immunology
Volume140
Issue number4
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Immunology

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