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15‐Deoxy‐Δ 12,14 ‐PGJ 2 , but not troglitazone, modulates IL‐1β effects in human chondrocytes by inhibiting NF‐κB and AP‐1 activation pathways
Author(s) -
Boyault Sandrine,
Simonin Marie-Agnès,
Bianchi Arnaud,
Compe Emmanuel,
Liagre Bertrand,
Mainard Didier,
Bécuwe Philippe,
Dauça Michel,
Netter Patrick,
Terlain Bernard,
Bordji Karim
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02614-x
Subject(s) - troglitazone , western blot , chemistry , proinflammatory cytokine , peroxisome proliferator activated receptor , nitric oxide synthase , nitric oxide , activator (genetics) , receptor , medicine , endocrinology , inflammation , biochemistry , biology , organic chemistry , gene
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 J 2 (15d‐PGJ 2 ), 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‐PGJ 2 inhibited NF‐κB 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 PPARγ‐independent.