Involvement of protein kinase C in IL-1β-induced expression of cyclooxygenase-2 in human gingival fibroblasts

Interleukin-1beta (IL-1beta) stimulates expression of the highly inducible enzyme cyclooxygenase-2 (COX-2) via activation of nuclear factor kappaB (NFkappaB), and consequently provokes prostaglandin E(2) (PGE(2)) synthesis, which induces inflammatory responses. In this study, the contribution of protein kinase C (PKC) to IL-1beta-induced PGE(2) synthesis in human gingival fibroblasts was investigated. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated PGE(2) release and COX-2 mRNA expression, as shown in human gingival fibroblasts stimulated by IL-1beta. However, PMA showed only a weak effect on the formation of COX-2-NFkappaB DNA-protein complex, whereas IL-1beta had a clearly stimulatory effect. In cells in which PMA-dependent PKC was down-regulated, PMA failed to induce the formation of NFkappaB DNA-protein complex and reduced the release of PMA-induced PGE(2), whereas IL-1beta stimulated the formation of COX-2-NFkappaB DNA-protein complex and PGE(2) release. The atypical PKC (aPKC) inhibitor Gö6983 clearly suppressed the formation of COX-2-NFkappaB DNA-protein complex and PGE(2) release stimulated by IL-1beta but not the inhibitor of conventional PKC (cPKC) and the novel PKC (nPKC) inhibitor Gö6976. These observations suggest that aPKC is involved in IL-1beta-induced PGE(2) synthesis, which is controlled by transcription of the COX-2 gene via the NFkappaB-dependent pathway in human gingival fibroblasts.