Cyclooxygenase expression is elevated in retinoic acid-differentiated U937 cells.
Cyclooxygenase (COX) is the rate-limiting enzyme for the biosynthesis of prostaglandins in monocytes/macrophages. The COX-1 is constitutively expressed in most tissues and may be involved in cellular homeostasis, whereas the COX-2 is an inducible enzyme that may play an important role in inflammation and mitogenesis. When U937 monocytic cells were incubated with retinoic acid (RA) for 48 h, cell differentiation took place with concomitant increases in prostaglandin E2 (PGE2) production and COX activity. In this study, the mechanism of RA (all-trans- or 9-cis-RA)-induced enhancement of PGE2 biosynthesis in U937 cells was examined. Treatment of cells with all-trans- or 9-cis-RA up to 48 h caused an increase in PGE2 production in a time- and dose-dependent manner. Both RA isomers caused the enhancement of PGE2 production and the up-regulation of COX-1 expression at the protein and mRNA levels. The increase in COX-1 mRNA was found to precede the increase in COX-1 protein expression. Interestingly, the COX-2 protein and COX-2 mRNA were not detected in U937 cells, and their levels remained undetectable during the entire course of RA treatment. We conclude that treatment of U937 cells by RA for 48 h caused the initiation of cell differentiation, which was found to be concomitant with a significant increase in PGE2 production mediated via the up-regulation of COX-1 mRNA and protein expression.
Jiang
Yan J
YJ
Centre for Research and Treatment of Atherosclerosis, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada R3E 0W3.
Xu
Tian-Rui
TR
Lu
Biao
B
Mymin
David
D
Kroeger
Edwin A
EA
Dembinski
Tom
T
Yang
Xi
X
Hatch
Grant M
GM
Choy
Patrick C
PC
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D000970:Antineoplastic Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D014212:Tretinoin; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone