Article (Scientific journals)
TNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apoptosis via nuclear factor-kappaB
Relic, Biserka; Bentires-Alj, Mohamed; Ribbens, Clio et al.
2002In Laboratory Investigation, 82 (12), p. 1661-1672
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Keywords :
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.
Disciplines :
Rheumatology
Author, co-author :
Relic, Biserka ;  Université de Liège - ULiège > Rhumatologie
Bentires-Alj, Mohamed
Ribbens, Clio ;  Université de Liège - ULiège > Rhumatologie
Franchimont, Nathalie
Guerne, Pierre-Andre
Benoit, Valerie
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 :
TNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apoptosis via nuclear factor-kappaB
Publication date :
2002
Journal title :
Laboratory Investigation
ISSN :
0023-6837
eISSN :
1530-0307
Publisher :
Lippincott Williams & Wilkins, Hagerstown, United States - Maryland
Volume :
82
Issue :
12
Pages :
1661-1672
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 29 June 2011

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