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

FEBS Letters

Compe, Emmanuel¹  Liagre, Bertrand³  Simonin, Marie-Agnès³  Mainard, Didier³  Dauça, Michel²  Boyault, Sandrine³  Bianchi, Arnaud²  Netter, Patrick³  Bécuwe, Philippe²  Bordji, Karim³  Terlain, Bernard³ 

[1] Unité INSERM 476, Faculté de Médecine, Marseille, France;Laboratoire de Biologie Cellulaire du Développement, Université Henri Poincaré, Vandœuvre-lès-Nancy, France;Laboratoire de Pharmacologie, UMR 7561 CNRS-Université Henri Poincaré Nancy I, Faculté de Médecine, 54505 Vandœuvre-lès-Nancy, France

关键词: Peroxisome proliferator-activated receptor;    Human chondrocyte;    Interleukin-1β;    15-Deoxy-Δ12;    14-PGJ2;    Nuclear factor-κB;    Activator protein-1;    IL-1;    interleukin-1;    PPAR;    peroxisome proliferator-activated receptor;    15d-PGJ2;    15-deoxy-Δ12;    14-prostaglandin J2;    iNOS;    inductible nitric oxide synthase;    COX-2;    cyclooxygenase-2;    AP-1;    activator protein-1;    NF-κB;    nuclear factor-κB;    FCS;    fetal calf serum;    EMSA;    electrophoretic mobility shift assay;   

DOI  :  10.1016/S0014-5793(01)02614-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The activation of peroxisome proliferator-activated receptor γ (PPARγ) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1β (IL-1β) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARγ ligands to modulate IL-1β effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARγ expression was decreased by IL-1β. 15-Deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂), in contrast to troglitazone, was highly potent to counteract IL-1β-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-κB 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 PPARγ-independent.

【 授权许可】

Unknown