Basic fibroblast growth factor induces interleukin-6 synthesis in osteoblasts: autoregulation by protein kinase C.
We previously reported that basic fibroblast growth factor (bFGF) stimulates both phospholipases C and D via independent pathways in osteoblastlike MC3T3-E1 cells. In this study, we investigated the effect of bFGF on interleukin-6 (IL-6) synthesis in these cells. bFGF stimulated the IL-6 synthesis dose-dependently in the range between 1 and 30 ng/ml. The depletion of extracellular Ca2+ by EGTA suppressed the bFGF-induced IL-6 synthesis. TMB-8, an inhibitor of intracellular Ca2+ mobilization, also inhibited the IL-6 synthesis by bFGF. bFGF stimulated the Ca2+ influx from extracellular space. Genistein, a tyrosine kinase inhibitor, suppressed the bFGF-induced Ca2+ influx. Staurosporine, an inhibitor for protein kinases, enhanced the bFGF-induced IL-6 synthesis. Calphostin C, a highly potent and specific inhibitor for protein kinase C (PKC), also enhanced the IL-6 synthesis by bFGF. The bFGF-induced IL-6 synthesis was amplified in PKC down-regulated cells. U-73122, a phospholipase C inhibitor, enhanced the bFGF-induced IL-6 synthesis. Propranolol, a phosphatidic acid phosphohydrolase inhibitor, also enhanced the IL-6 synthesis by bFGF. These results strongly suggest that bFGF stimulates IL-6 synthesis, which depends on intracellular Ca2+ mobilization in osteoblastlike cells, and that the IL-6 synthesis by bFGF is autoregulated due to PKC activation.
Kozawa
O
O
Department of Pharmacology, Gifu University School of Medicine, Japan.
Suzuki
A
A
Uematsu
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D012886:Skull / Q000166:cytology; D019311:Staurosporine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D004963:Estrenes; D015850:Interleukin-6; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013565:Sympatholytics; D016222:Fibroblast Growth Factor 2; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011433:Propranolol; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D; D019311:Staurosporine; C058819:calphostin C; D002118:Calcium