15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts
15-deoxy-delta(12,14)-prostaglandin J2; Annexin A5; Anti-Infective Agents; BAY 11-7085; Coloring Agents; I-kappa B Proteins; Immunologic Factors; Leupeptins; Multienzyme Complexes; NF-kappa B; Nitriles; Receptors, Cytoplasmic and Nuclear
Abstract :
[en] We have previously shown that nuclear factor-kappaB inhibition by adenovirus
expressing mutated IkappaB-alpha or by proteasome inhibitor increases human
articular chondrocytes sensibility to apoptosis. Moreover, the nuclear
factor-kappaB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat
adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this
work, we show that BAY 11-7085 but not the proteasome inhibitor MG-132 induced a
rapid and sustained phosphorylation of extracellular signal-regulated kinases
(ERK1/2) in human articular chondrocytes. The level of ERK1/2 phosphorylation
correlated with BAY 11-7085 concentration and chondrocyte apoptosis.
15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and its precursor prostaglandin
(PG) D2 but not PGE2 and PGF2alpha rescued chondrocytes from BAY 11-7085-induced
apoptosis. 15d-PGJ2 markedly inhibited BAY 11-7085-induced phosphorylation of
ERK1/2. BAY 11-7085 also induced ERK1/2 phosphorylation and apoptosis in human
synovial fibroblasts, and these reactions were down-regulated by 15d-PGJ2.
Further analysis in synovial fibroblasts showed that only molecules that
suppressed BAY 11-7085-induced phosphorylation of ERK1/2 (i.e. 15d-PGJ2, PGD2,
and to a lesser extent, MEK1/2 inhibitor UO126, but not prostaglandins E2 and
F2alpha or peroxisome proliferator-activated receptor-gamma agonist ciglitazone)
were able protect cells from apoptosis. These results suggested that the
antiapoptotic effect of 15d-PGJ2 on chondrocytes and synovial fibroblasts might
involve inhibition of ERK1/2 phosphorylation.
Disciplines :
Rheumatology
Author, co-author :
Relic, Biserka ; Université de Liège - ULiège > Rhumatologie
Benoit, Valerie
Franchimont, Nathalie
Ribbens, Clio ; Université de Liège - ULiège > Rhumatologie
Gillet, Philippe ; Université de Liège - ULiège > Chirurgie appareil locomoteur
Merville, Marie-Paule ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine
Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie
Language :
English
Title :
15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts
Publication date :
2004
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
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