Involvement of ERK and protein tyrosine phosphatase signaling pathways in EGCG-induced cyclooxygenase-2 expression in raw 264.7 cells

Prostaglandins play regulatory roles in a variety of physiological and path ological processes in immune response and inflammation. Epigallocatechin-3- gallate (EGCG) is known to potent antitumor agent with antioxidant property . We first investigated the effect of EGCG on the production of prostagland in E-2 (PGE(2)) and the expression of cyclooxygenase-2 (COX-2), the rate-li miting enzyme in the synthesis of PGE(2), using macrophage cell line, Raw26 4.7. Our results showed that COX-2 expression and PGE(2) production are upr egulated by EGCG treatment and that this induction of COX-2 is regulated in part at the transcriptional level. In addition, we demonstrated the signal transduction pathway of mitogen-activated protein kinase (MAP kinase) in E GCG-mediated COX-2 expression. The MEK inhibitor (PD098059) prevented EGCG- induced COX-2 expression, whereas sodium orthovanadate (protein-tyrosine ph osphatase inhibitor) significantly enhanced COX-2 expression and PGE2 produ ction. These results suggest that EGCG mediated COX-2 expression and PGE(2) production is associated with the activation of both the ERK and protein-t yrosine phosphatase signaling pathways. (C) 2001 Academic Press.