Interleukin-1β activates protein kinase Cζ in renal mesangial cells. Potential role in prostaglandin E2 up-regulation

Danuta M. Rzymkiewicz, Toshifumi Tetsuka, Dorit Daphna-Iken, Sunil Srivastava, Aubrey R. Morrison

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Protein kinase C (PKC) plays a role in signal transduction mediated by interleukin-1β (IL-1β) 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-1β 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 PGE2 formation by IL-1β. Furthermore, incubation of mesangial cells with IL-1β causes translocation of PKCζ 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-1β-stimulated binding of nuclear extracts to the NFκB motif. In contrast, calphostin C inhibited binding to the κB motif in a dose-dependent manner. Finally, antisense oligonucleotides to PKCζ partially inhibited the IL-1β-induced PGE2 formation while control sense oligonucleotides were without effect. Taken together, these data suggest that FKCζ is involved in the IL-1β signaling responses.

Original languageEnglish
Pages (from-to)17241-17246
Number of pages6
JournalJournal of Biological Chemistry
Issue number29
StatePublished - 1996


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