15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.
Fiche publication
Date publication
juillet 2001
Journal
FEBS letters
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MAINARD Didier
Tous les auteurs :
Boyault S, Simonin MA, Bianchi A, Compe E, Liagre B, Mainard D, Bécuwe P, Dauça M, Netter P, Terlain B, Bordji K
Lien Pubmed
Résumé
The activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARgamma ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was highly potent to counteract IL-1beta-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-PGJ2 inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d-PGJ2 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-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.
Mots clés
Active Transport, Cell Nucleus, drug effects, Blotting, Western, Cell Nucleus, drug effects, Cells, Cultured, Chondrocytes, cytology, Chromans, pharmacology, Cyclooxygenase 2, DNA, genetics, Enzyme Induction, drug effects, Gene Expression Regulation, drug effects, Humans, Interleukin-1, antagonists & inhibitors, Isoenzymes, genetics, Ligands, Membrane Proteins, NF-kappa B, metabolism, Nitric Oxide, metabolism, Nitric Oxide Synthase, genetics, Nitric Oxide Synthase Type II, Prostaglandin D2, analogs & derivatives, Prostaglandin-Endoperoxide Synthases, genetics, Prostaglandins, biosynthesis, Protein Binding, drug effects, Proteoglycans, biosynthesis, Proto-Oncogene Proteins c-jun, metabolism, RNA, Messenger, genetics, Receptors, Cytoplasmic and Nuclear, genetics, Signal Transduction, drug effects, Thiazoles, pharmacology, Thiazolidinediones, Transcription Factor AP-1, metabolism, Transcription Factors, genetics
Référence
FEBS Lett.. 2001 Jul;501(1):24-30