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 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 PGE(2) 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.
Copyright 2001 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Catechin / analogs & derivatives
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Catechin / pharmacology*
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Cell Line
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Cyclooxygenase 2
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Dinoprostone / biosynthesis
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Isoenzymes / biosynthesis*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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MAP Kinase Signaling System / drug effects
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Macrophages / drug effects
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Macrophages / enzymology*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology*
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Protein Tyrosine Phosphatases / physiology*
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RNA, Messenger / biosynthesis
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Signal Transduction* / drug effects
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Up-Regulation
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Vanadates / pharmacology
Substances
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Enzyme Inhibitors
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Flavonoids
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Isoenzymes
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RNA, Messenger
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Vanadates
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Catechin
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epigallocatechin gallate
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Protein Tyrosine Phosphatases
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Dinoprostone
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one