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

Sumi Nakao, Daisuke Inoue
2009 Journal of Oral Science  
Interleukin-1β (IL-1β) stimulates e x p re s s i o n o f t h e h i g h l y i n d u c i b l e e n z y m e cyclooxygenase-2 (COX-2) via activation of nuclear factor kappaB (NFκB), 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-1β-induced PGE 2 synthesis in human gingival fibroblasts was investigated. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated PGE 2 release
more » ... lated PGE 2 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 DNAprotein 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 PGE 2 , whereas IL-1β stimulated the formation of COX-2-NFκB DNA-protein complex and PGE 2 release. The atypical PKC (aPKC) inhibitor Gö6983 clearly suppressed the formation of COX-2-NFκB DNA-protein complex and PGE 2 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 PGE 2 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)
doi:10.2334/josnusd.51.417 pmid:19776509 fatcat:s2pw2h5sl5dt3byf32ccddzlfi