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

✍ Scribed by Beomsue Kim; Jee-Hyung Lee; Myung-Soon Yang; Ilo Jou; Eun-Hye Joe

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 403 KB
• Volume: 86
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21593

✦ Synopsis

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. V