15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Boyault S,Simonin MA,Bianchi A,Compe E,Liagre B,Mainard D,Bécuwe P,Dauça M,Netter P,Terlain B,Bordji K

doi

10.1016/s0014-5793(01)02614-x

keywords:

subject

Has Abstract

pub_date

2001-07-13 00:00:00

pages

24-30

issue

1

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(01)02614-X

journal_volume

501

pub_type

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