Involvement of protein kinase A and C in the production of interleukin-1 alpha-induced prostaglandin E2 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 E2 (PGE2). 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-1-induced PGE2 production in MC3T3-E1 cells, as did staurosporine, 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 PGE2, as did the PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). However, 8-Br-cAMP and TPA acted synergistically to induce PGE2 production equal to that of IL-1. These observations suggest that activation of both PKA and PKC are involved in IL-1-induced PGE2 production in MC3T3-E1 cells.
Iitaka
M
M
Department of Internal Medicine 4, Saitama Medical School, Japan.
Kitahama
S
S
Ishii
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; D007375:Interleukin-1; D007546:Isoquinolines; D010879:Piperazines; D011758:Pyrroles; D011994:Recombinant Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; C057416:KT 5720; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin