Prostaglandin F2alpha stimulates interleukin-6 synthesis via activation of PKC in osteoblast-like cells.
In previous studies, we reported that prostaglandin F2alpha (PGF2alpha) stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of PGF2alpha on synthesis of interleukin-6 (IL-6) and the involvement of protein kinase C (PKC) activation in the IL-6 synthesis in these cells. PGF2alpha significantly stimulated IL-6 synthesis in a dose-dependent manner in the range between 10 nM and 10 microM. A PKC-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), induced IL-6 synthesis. On the contrary, 4alpha-phorbol 12,13-didecanoate, a PKC-nonactivating phorbol ester, had no effect. The synthesis of IL-6 stimulated by a combination of PGF2alpha and TPA was not additive. Staurosporine, an inhibitor for protein kinases that suppressed the TPA-induced IL-6 synthesis, significantly inhibited the PGF2alpha-induced IL-6 synthesis. Calphostin C, a highly specific PKC inhibitor, also suppressed the PGF2alpha-stimulated synthesis of IL-6. The effect of PGF2alpha on IL-6 synthesis in PKC-downregulated cells was much weaker than that in intact cells. These results strongly suggest that PGF2alpha induces IL-6 synthesis via PKC activation in osteoblast-like cells.
Kozawa
O
O
Department of Pharmacology, Gifu University School of Medicine, Japan.
Suzuki
A
A
Tokuda
H
H
Uematsu
T
T
D000818:Animals; D002460:Cell Line; D015237:Dinoprost / Q000494:pharmacology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009281:Naphthalenes; D015237:Dinoprost; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate