Mechanism of prostaglandin D 2-stimulated heat shock protein 27 induction in osteoblasts

Abstract

We previously showed that prostaglandin D 2 (PGD 2) stimulates activation of protein kinase C (PKC). We investigated whether PGD 2 stimulates the induction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E1 cells and the mechanism underlying the induction. PGD 2 increased the levels of HSP27 while having little effect on HSP70 levels. PGD 2 stimulated the accumulation of HSP27 dose dependently in the range between 10 nM and 10 μM. PGD 2 induced an increase in the levels of mRNA for HSP27. The PGD 2-stimulated accumulation of HSP27 was reduced by staurosporine or calphostin C, inhibitors of PKC. PGD 2 induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumulation induced by PGD 2 was significantly suppressed by PD98059, an inhibitor of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor of p38 MAP kinase. Calphostin C suppressed the PGD 2-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. PD98059 or SB203580 suppressed the PGD 2-increased levels of mRNA for HSP27. These results strongly suggest that PGD 2 stimulates HSP27 induction through p44/p42 MAP kinase activation and p38 MAP kinase activation in osteoblasts and that PKC acts at a point upstream from both the MAP kinases.