15-deoxy-Δ12,14-PGJ2, but not troglitazone, modulates IL-1β effects in human chondrocytes by inhibiting NF-κB and AP-1 activation pathways

The activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to inhibit the production and the effects of proinflammatory cytokines, Since interleukin-1 beta (IL-1 beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPAR gamma ligands to modulate IL-1 beta effects on human chondrocytes, RT-PCR and Western blot analysis revealed that PPAR gamma expression was decreased by IL-1 beta 15-Deoxy-Delta (12,14)-prostaglandin J(2) (15d-PGJ(2)), in contrast to troglitazone, was highly potent to counteract IL-1 beta -induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO production and the decrease in proteoglycan synthesis, Western blot and gel-shift analyses demonstrated that 15d-PCJ(2) inhibited NF-kappaB activation, while troglitazone was ineffective, Although 15d-PGJ(2) attenuated activator protein-1 binding on the DNA, it potentiated c-jun migration in the nucleus, The absence or the low effect of troglitazone suggests that 15d-PGJ(2) action in human chondrocytes is mainly PPAR gamma -independent, (C) 2001 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.