Sphingosine modulates interleukin-6 synthesis in osteoblasts.
We previously reported that prostaglandin (PG)E1 and PGF2alpha induce the synthesis of interleukin-6 (IL-6) via activation of protein kinase (PK)A and PKC, respectively, in osteoblast-like MC3T3-E1 cells. In addition, we have shown that basic fibroblast growth factor (bFGF) elicits IL-6 synthesis through intracellular Ca2+ mobilization in these cells and that tumor necrosis factor-alpha (TNF) induces IL-6 synthesis through sphingosine 1-phosphate produced by sphingomyelin hydrolysis. In the present study, among sphingomyelin metabolites, we examined the effect of sphingosine on IL-6 synthesis induced by various agonists in MC3T3-E1 cells. Sphingosine inhibited the IL-6 synthesis induced by PGF2alpha or 12-O-tetradecanoylphorbol-13-acetate, an activator of PKC. Sphingosine suppressed the PGE1-induced IL-6 synthesis. The IL-6 synthesis induced by cholera toxin, forskolin, or dibutyryl cAMP was inhibited by sphingosine. Sphingosine inhibited the IL-6 synthesis induced by bFGF or A23187. However, sphingosine did not affect the IL-6 synthesis induced by interleukin-1. On the contrary, sphingosine enhanced the TNF-induced IL-6 synthesis. DL-threo-Dihydrosphingosine, an inhibitor of sphingosine kinase, reduced the enhancement by sphingosine as well as the TNF-effect. These results indicate that sphingosine modulates the IL-6 synthesis stimulated by various agonists in osteoblasts.
Department of Pharmacology, Gifu University School of Medicine, Japan.
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Kozawa
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Tokuda
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Matsuno
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Uematsu
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D000001:Calcimycin; D003994:Bucladesine; D002772:Cholera Toxin; D015237:Dinoprost; D000527:Alprostadil; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate