15d-PGJ(2) is acting as a 'dual agent' on the regulation of COX-2 expression in human osteoarthritic chondrocytes.
The PGD(2) metabolite 15-deoxy-delta12,14 PGJ(2) (15d-PGJ(2)), a potent peroxisome proliferator-activated receptor gamma (PPARgamma) activator, has recently received attention for its potential antiinflammatory effects, but its effect on the cyclooxygenase-2 (COX-2) production is still under debate. We investigated the effect of 15d-PGJ(2) on COX-2 and prostaglandin E(2) (PGE(2)) production in the absence or the presence of interleukin-1beta (IL-1beta) in human osteoarthritic chondrocytes.Data showed that, as expected, IL-1beta induced both COX-2 and PGE(2) production. The addition of 15d-PGJ(2) completely blocked (by 93%) the IL-1beta-induced PGE(2) synthesis, whereas COX-2 level was only partially reduced (by 72%). Interestingly in the absence of any COX-2 inducer, 15d-PGJ(2) up-regulated COX-2 expression without concomitant elevation of PGE(2) synthesis. This study showed that the PPARgamma agonist, 15d-PGJ(2), exerts a dual effect on COX-2 production. The mechanisms by which 15d-PGJ(2) favors COX-2 production will be discussed.
Fahmi
H
H
Osteoarthritis Research Unit, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Quebec, Canada.
Pelletier
J-P
JP
Mineau
F
F
Martel-Pelletier
J
J
D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D010544:Peroxidases / Q000096:biosynthesis*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D015854:Up-Regulation
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2