15d-PGJ2 is acting as a 'dual agent' on the regulation of COX-2 expression in human osteoarthritic chondrocytes

Abstract

The PGD2 metabolite 15-deoxy-delta 12,14 PGJ2, (15d-PGJ2), a potent peroxisome proliferator-activated receptor γ (PPARγ) activator, has recently received attention for its potential anti-inflammatory effects, but its effect on the cyclooxygenase-2 (COX-2) production is still under debate. We investigated the effect of 15d-PGJ2 on COX-2 and prostaglandin E2 (PGE2) production in the absence or the presence of interleukin-1β (IL-1β) in human osteoarthritic chondrocytes. Data showed that, as expected, IL-1β induced both COX-2 and PGE2 production. The addition of 15d-PGJ2 completely blocked (by 93%) the IL-1β-induced PGE2 synthesis, whereas COX-2 level was only partially reduced (by 72%). Interestingly in the absence of any COX-2 inducer, 15d-PGJ2 up-regulated COX-2 expression without concomitant elevation of PGE2 synthesis. This study showed that the PPARγ agonist, 15d-PGJ2, exerts a dual effect on COX-2 production. The mechanisms by which 15d-PGJ2 favors COX-2 production will be discussed. © 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.