(Received for publication, April 16, 1996)

From the Departments of ^§ Medicine and Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110

Protein kinase C (PKC) plays a role in signal transduction mediated by interleukin-1 (IL-1) leading to the increase in prostaglandin E₂ (PGE₂) production. In the present study we suggest that there are at least two distinct PKC isotypes involved in the signaling mechanism. Staurosporine potentiated the effect of IL-1 on coxII mRNA expression while calphostin C totally inhibited mRNA expression. The down-regulation of PKC by growing mesangial cells in the presence of phorbol 12-myristate 13-acetate for 24 h failed to modify the up-regulated response in PGE₂ formation by IL-1. Furthermore, incubation of mesangial cells with IL-1 causes translocation of PKC from cytosol to a presumed membrane compartment, and this translocation phenomenon was not inhibited by incubating the cells with staurosporine but was inhibited with calphostin C. Gel retardation assays also demonstrated that staurosporine did not inhibit the IL-1-stimulated binding of nuclear extracts to the NFB motif. In contrast, calphostin C inhibited binding to the B motif in a dose-dependent manner. Finally, antisense oligonucleotides to PKC partially inhibited the IL-1-induced PGE₂ formation while control sense oligonucleotides were without effect. Taken together, these data suggest that PKC is involved in the IL-1 signaling responses.

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