Involvement of ERK and Protein Tyrosine Phosphatase Signaling Pathways in EGCG-Induced Cyclooxygenase-2 Expression in Raw 264.7 Cells

Abstract

Prostaglandins play regulatory roles in a variety of physiological and pathological 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 prostaglandin E2 (PGE2) and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGE2, using macrophage cell line, Raw264.7. Our results showed that COX-2 expression and PGE2 production are upregulated 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 EGCG-mediated COX-2 expression. The MEK inhibitor (PD098059) prevented EGCG-induced COX-2 expression, whereas sodium orthovanadate (protein-tyrosine phosphatase inhibitor) significantly enhanced COX-2 expression and PGE2 production. These results suggest that EGCG mediated COX-2 expression and PGE2 production is associated with the activation of both the ERK and protein-tyrosine phosphatase signaling pathways.

Keywords EGCG; COX-2; signal transduction; prostaglandin, COX-2 promoter