Interleukin-1 beta activates protein kinase C zeta in renal mesangial cells - Potential role in prostaglandin E(2) up-regulation

Protein kinase C (PKC) plays a rob in signal transduction mediated by interleukin-1 beta (IL-1 beta) leading to the increase in prostaglandin E(2) (PGE(2)) 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 beta 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 upregulated response in PGE(2) formation by IL-1 beta. Furthermore, incubation of mesangial cells with IL-1 beta causes translocation of PKC zeta 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 beta-stimulated binding of nuclear extracts to the NF kappa B motif. In contrast, calphostin C inhibited binding to the kappa B motif in a dose-dependent manner. Finally, antisense oligonucleotides to PKC zeta partially inhibited the IL-1 beta-induced PGE(2) formation while control sense oligonucleotides were without effect. Taken together, these data suggest that PKC zeta is involved in the IL-1 beta signaling responses.