ORBi: Relic Biserka - 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

Reference : 15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellula...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Rheumatology
	To cite this reference:	http://hdl.handle.net/2268/94569

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
Language :	English
Author, co-author :	Relic, Biserka [Université de Liège - ULg > > Rhumatologie >]
	Benoit, Valerie [ > > ]
	Franchimont, Nathalie [ > > ]
	Ribbens, Clio [Université de Liège - ULg > > Rhumatologie >]
	Kaiser, Marie-Joëlle [Université de Liège - ULg > > Rhumatologie >]
	Gillet, Philippe [Université de Liège - ULg > > Chirurgie appareil locomoteur >]
	Merville, Marie-Paule [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
	Bours, Vincent [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine >]
	Malaise, Michel [Université de Liège - ULg > Département des sciences cliniques > Rhumatologie >]
Publication date :	2004
Journal title :	Journal of Biological Chemistry
Publisher :	American Society for Biochemistry and Molecular Biology
Volume :	279
Issue/season :	21
Pages :	399-403
Audience :	International
ISSN :	0021-9258
e-ISSN :	1083-351X
City :	Baltimore
Country :	MD
Keywords :	[en] 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.
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/94569

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