4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid and diazepinylbenzoic-acid

All-trans retinoic acid (ATRA) increases the expression of COX-1 and COX-2 and the production of PGE2, a prostaglandin with anti-inflammatory effects in human mesangial cells (MC). COX-2 increased through a transcriptional mechanism independent of retinoic acid receptors (RAR) and retinoid X receptors (RXR) and dependent on extracellular regulated kinase-1/2 (ERK1/2), that became phosphorylated 5 min after ATRA addition. Here, in rat MC, ATRA also upregulated COX isoenzymes and PGE2 production, but not in the same way as in human MC: (1) PGE2 production increased only slightly; (2) RAR and RXR were involved in the transcriptional upregulation of COX-2 by ATRA since the RAR-pan-antagonist AGN193109 or the RXR-pan-antagonist HX531 abolished the induction of COX-2 mRNA whereas the RAR-pan-agonist TTNPB or the RXR-pan-agonist AGN194204 induced expression of COX-2, and (3) ERK1/2 phosphorylation, though important for COX-2 upregulation, took more than 1 h. Therefore the regulation of COX by ATRA exhibits striking differences between human and rat MC.

Topics: Animals; Benzoates; Biphenyl Compounds; Blotting, Northern; Blotting, Western; Cell Line; Cyclooxygenase 1; Cyclooxygenase 2; Dactinomycin; Dinoprostone; Dose-Response Relationship, Drug; Flavonoids; Humans; Interleukin-1beta; Male; MAP Kinase Kinase 1; Mesangial Cells; Prostaglandin-Endoperoxide Synthases; Protein Synthesis Inhibitors; Quinolines; Rats; Rats, Sprague-Dawley; Retinoid X Receptors; Retinoids; RNA, Messenger; Time Factors; Tretinoin; Up-Regulation