Upregulation of cyclooxygenases by retinoic acid in rat mesangial cells.
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.
Alique
Matilde
M
Department of Physiology, University of Alcala, Alcala de Henares, Madrid, Spain.
Lucio-Cazaña
Francisco Javier
FJ
Moreno
Victoria
V
Xu
Qihe
Q
Konta
Tsuneo
T
Nakayama
Kenji
K
Furusu
Akira
A
Sepulveda
Juan C
JC
Kitamura
Masanori
M
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D047488:Retinoid X Receptors / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
C487202:AGN193198; D001565:Benzoates; D001713:Biphenyl Compounds; D005419:Flavonoids; D053583:Interleukin-1beta; D011500:Protein Synthesis Inhibitors; D011804:Quinolines; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D012176:Retinoids; C438269:diazepinylbenzoic acid; D003609:Dactinomycin; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048369:MAP Kinase Kinase 1; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one