(-)-Epigallocatechin gallate inhibits prostaglandin D2-stimulated HSP27 induction via suppression of the p44/p42 MAP kinase pathway in osteoblasts

We previously reported that prostaglandin D-2 (PGD(2)) stimulates heat shock protein 27 (HSP27) induction through p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (INK) and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether (-)-epigallocatechin gallate (EGCG), the major polyphenol found in green tea, affects the induction of HSP27 in these cells and the mechanism. EGCG significantly reduced the HSP27 induction stimulated by PGD(2) without affecting the levels of HSP70. The PGD(2)-induced phosphorylation of p38 MAP kinase or SAPK/JNK was not affected by EGCG. On the contrary, EGCG markedly suppressed the PGD(2)-induced phosphorylation of p44/p42 MAP kinase and MEKI/2. However, the PGD(2)-induced phosphorylation of Raf-1 was not inhibited by EGCG. These results strongly suggest that EGCG suppresses the PGD(2)-Stirmilated induction of HSP27 at the point between Raf-1 and MEK1/2 in osteoblasts. (C) 2007 Elsevier Ltd. All rights reserved.