Abstract
We previously showed that sphingosine inhibits prostaglandin F 2α (PGF 2α)-stimulated interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of sphingosine on phospholipase C-catalyzing phosphoinositide hydrolysis induced by PGF 2α in these cells. Sphingosine inhibited the inositol phosphates formation by PGF 2α or NaF, a GTP-binding protein activator. Sphingosine induced the phosphorylation of p38 mitogen-activated protein (MAP) kinase but did not affect the phosphorylation of p42/p44 MAP kinase. SB203580 and PD169316, inhibitors of p38 MAP kinase, rescued the inhibitory effect of sphingosine on the formation of inositol phosphates by PGF 2α or NaF. These results indicate that sphingosine inhibits PGF 2α-induced phosphoinositide hydrolysis by phospholipase C via p38 MAP kinase in osteoblasts.
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