Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 286, Issue 4, Pages 721-725Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/bbrc.2001.5415
Keywords
EGCG; COX-2; signal transduction; prostaglandin; COX-2 promoter
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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 E-2 (PGE(2)) and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGE(2), using macrophage cell line, Raw264.7. Our results showed that COX-2 expression and PGE(2) 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 PGE(2) production is associated with the activation of both the ERK and protein-tyrosine phosphatase signaling pathways. (C) 2001 Academic Press.
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