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

We previously showed that prostaglandin D-2 (PGD(2)) stimulates activation of protein kinase C (PKC). We investigated whether PGD(2) stimulates the in duction of heat shock protein (HSP) 27 and HSP70 in osteoblast-like MC3T3-E 1 cells and the mechanism underlying the induction. PGD(2) increased the le vels 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 muM. PGD(2) induced an increase in the levels of mRNA for HSP27. The PGD (2)-stimulated accumulation of HSP27 was reduced by staurosporine or calpho stin C, inhibitors of PKC. PGD(2) induced the phosphorylation of p44/p42 mi togen-activated protein (MAP) kinase and p38 MAP kinase. The HSP27 accumula tion induced by PGD(2) was significantly suppressed by PD98059, an inhibito r of the upstream kinase of p44/p42 MAP kinase, or SB203580, an inhibitor o f p38 MAP kinase. Calphostin C suppressed the PGD(2)-induced phosphorylatio n 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 sugge st that PGD(2) stimulates HSP27 induction through p44/p42 MAP kinase activa tion and p38 MAP kinase activation in osteoblasts and that PKC acts at a po int upstream from both the MAP kinases. (C) 2001 Elsevier Science Inc. All rights reserved.