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Retinoic acid enhances prostaglandin E 2 production through increased expression of cyclooxygenase‐2 and microsomal prostaglandin E synthase‐1 in rat brain microglia
Author(s) -
Kim Beomsue,
Lee JeeHyung,
Yang MyungSoon,
Jou Ilo,
Joe EunHye
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21593
Subject(s) - cyclooxygenase , prostaglandin , retinoic acid , atp synthase , chemistry , prostaglandin e2 , microsome , prostaglandin e , microglia , prostaglandin h2 , enzyme , biochemistry , endocrinology , medicine , biology , gene , inflammation
Retinoic acid (RA) is a well‐known antiinflammatory agent. In this study, we show that RA has a dual effect on cyclooxygenase‐2 (COX‐2) expression in inflammatory activated microglia, the resident brain macrophages. After treatment of microglia with LPS or thrombin, COX‐2 expression was induced in two phases, specifically, an initial increase at about 12 hr after stimulation followed by a decrease, and another increase at about 48–72 hr. However, PGE 2 and 15d‐PGJ 2 were detected at about 12 hr, and the levels continuously increased thereafter. Interestingly, all‐ trans retinoic acid (ATRA) suppressed the expression of early‐phase COX‐2 but augmented late‐phase COX‐2 and inhibited iNOS in the whole time sequence. ATRA enhanced PGE 2 production but had little effect on 15d‐PGJ 2 . Moreover, ATRA selectively up‐regulated the expression of a PGE 2 synthase, mPGES‐1, but had little effect on the PGD 2 synthase, H‐PGDS. The results collectively suggest that ATRA modulates microglial responses to inflammatory stimulators, particularly at the late phase, via enhancement of COX‐2 expression and PGE 2 production. © 2008 Wiley‐Liss, Inc.