[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
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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