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

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Interleukin-1β (IL-1β) stimulates expression of the highly inducible enzyme cyclooxygenase-2 (COX-2) via activation of nuclear factor kappaB (NFκB), and consequently provokes prostaglandin E2 (PGE2) synthesis, which induces inflammatory responses. In this study, the contribution of protein kinase C (PKC) to IL-1β-induced PGE2 synthesis in human gingival fibroblasts was investigated. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated PGE2 release and COX-2 mRNA expression, as shown in human gingival fibroblasts stimulated by IL-1β. However, PMA showed only a weak effect on the formation of COX-2-NFκB DNA-protein complex, whereas IL-1β had a clearly stimulatory effect. In cells in which PMA-dependent PKC was down-regulated, PMA failed to induce the formation of NFκB DNA-protein complex and reduced the release of PMA-induced PGE2, whereas IL-1β stimulated the formation of COX-2-NFκB DNA-protein complex and PGE2 release. The atypical PKC (aPKC) inhibitor Gö6983 clearly suppressed the formation of COX-2-NFκB DNA-protein complex and PGE2 release stimulated by IL-1β but not the inhibitor of conventional PKC (cPKC) and the novel PKC (nPKC) inhibitor Gö6976. These observations suggest that aPKC is involved in IL-1β-induced PGE2 synthesis, which is controlled by transcription of the COX-2 gene via the NFκB-dependent pathway in human gingival fibroblasts. (J Oral Sci 51, 417-423, 2009)
日本大学歯学部の論文