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Retinoic acid enhances prostaglandin E2 production through increased expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in rat brain microglia.

Authors
Kim, B; Lee, JH; Yang, MS; Jou, I; Joe, EH
Citation
Journal of neuroscience research, 86(6):1353-1360, 2008
Journal Title
Journal of neuroscience research
ISSN
0360-40121097-4547
Abstract
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.
MeSH terms
AnimalsAnti-Inflammatory Agents/pharmacology*Blotting, WesternBrain/drug effectsBrain/metabolismCells, CulturedCyclooxygenase 2/biosynthesis*Cyclooxygenase 2/drug effectsDinoprostone/biosynthesis*Enzyme-Linked Immunosorbent AssayInflammation/chemically inducedIntramolecular Oxidoreductases/biosynthesis*Lipopolysaccharides/toxicityMicroglia/drug effects*Microglia/metabolismMicrosomes/metabolismRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionThrombin/toxicityTretinoin/pharmacology*
DOI
10.1002/jnr.21593
PMID
18183617
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로조, 은혜
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