15-deoxy-Delta(12,14)-PGJ(2), but not troglitazone, modulates IL-1 beta effects in human chondrocytes by inhibiting NF-kappa B and AP-1 activation pathways

The activation of peroxisome proliferator-activated receptor gamma (PPAR ga mma) has been shown to inhibit the production and the effects of proinflamm atory cytokines, Since interleukin-1 beta (IL-1 beta) directly mediates car tilage degradation in osteoarthritis, we investigated the capability of PPA R gamma ligands to modulate IL-1 beta effects on human chondrocytes, RT-PCR and Western blot analysis revealed that PPAR gamma expression was decrease d by IL-1 beta 15-Deoxy-Delta (12,14)-prostaglandin J(2) (15d-PGJ(2)), in c ontrast to troglitazone, was highly potent to counteract IL-1 beta -induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO produ ction and the decrease in proteoglycan synthesis, Western blot and gel-shif t analyses demonstrated that 15d-PCJ(2) inhibited NF-kappaB activation, whi le troglitazone was ineffective, Although 15d-PGJ(2) attenuated activator p rotein-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) act ion in human chondrocytes is mainly PPAR gamma -independent, (C) 2001 Feder ation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.