Sphingosine 1-phosphate induces heat shock protein 27 via p38 mitogen-activated protein kinase activation in osteoblasts

We previously showed that sphingosine l-phosphate acts as a second messenger for tumor necrosis factor alpha-induced interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells and that the synthesis by sphingosine l-phosphate is dependent on p42/p44 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated the effect of sphingosine l-phosphate on the induction of heat shock protein 27 (HSP27) in MC3T3-E1 cells. Not C-2-ceramide, but sphingosine and sphingosine l-phosphate significantly induced HSP27 accumulation dose dependently in the range between 1 mu M and 30 mu M, DL-threo-dihydrosphingosine, an inhibitor of sphingosine kinase, markedly inhibited the sphingosine-induced HSP27 accumulation, Sphingosine 1-phosphate induced increase in the levels of the mRNA for HSP27, Sphingosine l-phosphate stimulated the phosphorylation of p38 MAP kinase, The sphingosine 1-phosphate-induced HSP27 accumulation was dose dependently suppressed by SB203580, an inhibitor of p38 MAP kinase, but not PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, SB203580 reduced the sphingosine 1-phosphate-induced increase of mRNA for HSP27. These results strongly suggest that sphingosine l-phosphate-stimulated HSP27 induction is mediated via p38 MAP kinase activation in osteoblasts.