ORBi: Relic Biserka - TNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apoptosis via nuclear factor-kappaB

Reference : TNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apopto...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Rheumatology
	To cite this reference:	http://hdl.handle.net/2268/94573

Title :	TNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apoptosis via nuclear factor-kappaB
Language :	English
Author, co-author :	Relic, Biserka [Université de Liège - ULg > > Rhumatologie >]
	Bentires-Alj, Mohamed [ > > ]
	Ribbens, Clio [Université de Liège - ULg > > Rhumatologie >]
	Franchimont, Nathalie [ > > ]
	Guerne, Pierre-Andre [ > > ]
	Benoit, Valerie [ > > ]
	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 :	2002
Journal title :	Laboratory Investigation : Journal of Technical Methods & Pathology
Publisher :	Lippincott Williams & Wilkins
Volume :	82
Issue/season :	12
Pages :	1661-1672
Audience :	International
ISSN :	0023-6837
e-ISSN :	1530-0307
City :	Hagerstown
Country :	MD
Keywords :	[en] Anti-Infective Agents ; Chromones ; Enzyme Inhibitors ; Isoenzymes ; Membrane Proteins ; Morpholines ; NF-kappa B ; Nitric Oxide Donors ; Tumor Necrosis Factor-alph
Abstract :	[en] TNF-alpha plays a key role in rheumatoid arthritis, but its effect on chondrocyte survival is still conflicting. In the present study, we tested how TNF-alpha influences chondrocyte survival in response to nitric oxide (NO)-related apoptotic signals, which are abundant during rheumatoid arthritis. Human primary articular chondrocytes or cartilage explants were pretreated with TNF-alpha for 24 hours and then treated with the proapoptotic NO donor sodium-nitro-prusside (SNP) for an additional 24 hours. TNF-alpha pretreatment markedly protected chondrocytes from SNP-induced cell death. Preincubation of chondrocytes with TNF-alpha inhibited both SNP-induced high-molecular weight DNA fragmentation and annexin V-FITC binding. Of interest, TNF-alpha induced persistent nuclear factor-kappaB (NF-kappaB)-DNA binding activity even in the presence of SNP, mirroring apoptosis protection effects. Both the TNF-alpha antiapoptotic effect and NF-kappaB-DNA binding activity were significantly inhibited by NF-kappaB inhibitors, Bay 11-7085, MG-132, and adenovirus-expressing mutated IkappaB-alpha. Phosphatidylinositol-3 kinase inhibitor LY 294002 also markedly inhibited the antiapoptotic effect of TNF-alpha. In primary chondrocytes, TNF-alpha induced expression of the antiapoptotic protein Cox-2, which persisted in the presence of SNP, and a specific Cox-2 inhibitor significantly blocked the TNF-alpha protective effect. We therefore conclude that TNF-alpha-mediated protection of chondrocytes from NO-induced apoptosis acts through NF-kappaB and requires Cox-2 activity.
Target :	Researchers ; Professionals
Permalink :	http://hdl.handle.net/2268/94573

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