INVOLVEMENT OF PROTEIN-KINASE-A AND PROTEIN-KINASE-C IN THE PRODUCTION OF INTERLEUKIN-1(ALPHA)-INDUCED PROSTAGLANDIN E(2) FROM MOUSE OSTEOBLAST-LIKE CELL-LINE, MC3T3-E1

Human recombinant interleukin-1 alpha (IL-1) stimulated the mouse osteoblast-like cell line, MC3T3-E1, to produce prostaglandin E(2) (PGE(2)). This was inhibited by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) in a dose-dependent manner. The protein kinase A (PKA)-specific inhibitor, KT5720, also inhibited the IL-l-induced PGE, production in MC3T3-E1 cells, as did staurosporin, a potent inhibitor of protein kinase C (PKC). The PKA activator, 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), weakly stimulated MC3T3-E1 cells to produce PGE(2), as did the PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). However, 8-Br-cAMP and TPA acted synergistically to induce PGE(2) production equal to that of IL-1. These observations suggest that activation of both PKA and PKC are involved in IL-1-induced PGE(2) production in MC3T3-E1 cells.