• BMB Reports
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• v.38 no.6
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• pp.633-638
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• 2005

Biosynthesis of prostanoids is regulated by three sequential enzymatic steps, namely phospholipase $A_2$ enzymes, cyclooxygenase (COX) enzymes, and various lineage-specific terminal prostanoid synthases. Prostaglandin E synthase (PGES), which isomerizes COX-derived $PGH_2$ specifically to $PGE_2$, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions. Two of them are membrane-bound enzymes and have been designated as mPGES-1 and mPGES-2. mPGES-1 is a perinuclear protein that is markedly induced by proinflammatory stimuli, is down-regulated by anti inflammatory glucocorticoids, and is functionally coupled with COX-2 in marked preference to COX-1. Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme. This enzyme is rather constitutively expressed in various cells and tissues and is functionally coupled with both COX-1 and COX-2. Cytosolic PGES (cPGES) is constitutively expressed in a wide variety of cells and is functionally linked to COX-1 to promote immediate $PGE_2$ production. This review highlights the latest understanding of the expression, regulation and functions of these three PGES enzymes.

• Journal of Life Science
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• v.18 no.2
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• pp.180-186
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• 2008

In this study, we examined the effects of the fermented soybeans by Bacillus subtilis (FSB) and the novel three-step fermented soybeans (TFS) on the expression and activity of COX-2 in human leukemic U937 cell model. Treatment of phorbol 12-myristate 13-acetate (PMA) significantly induced pro-inflammatory mediators such as COX-2 expression and prostaglandin $E_2\;(PGE_2)$ production, whereas the levels of COX-1 remained unchanged. However, pre-treatment with FSB and TFS significantly attenuated the PMA-induced COX-2 protein as well as mRNA, which was associated with inhibition of $PGE_2$ production. Moreover, TFS exerts a much better inhibitory activity than FSB against PMA-induced activation of COX-2 and production of $PGE_2$ in U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-inflammatory activity of FSB and TFS.