Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis synovial fibroblasts
1 Institut de Génétique Moléculaire de Montpellier, 1919 route de Mende, CNRS UMR5535, Montpellier, France
2 Service d'immuno-rhumatologie et Université Montpellier 1, 371 Ae du doyen Gaston Giraud, Montpellier, France
Arthritis Research & Therapy 2007, 9:R128 doi:10.1186/ar2342Published: 12 December 2007
Synovial hyperplasia in rheumatoid arthritis (RA) has been associated with apoptosis deficiency of RA fibroblast-like synoviocytes (FLSs). Celecoxib is a non-steroidal anti-inflammatory drug that has been demonstrated to induce apoptosis in some cellular systems. We have therefore examined the dose- and time-dependent effects of celecoxib on RA FLS viability. Treatment of RA FLSs with celecoxib for 24 hours reduced their viability in a dose-dependent manner. Analysis of celecoxib-treated RA FLSs for their content of apoptotic and necrotic cells by Annexin V staining and TO-PRO-3 uptake displayed only few apoptotic cells. Caspase 3, a key mediator of apoptosis, was not activated in celecoxib-treated RA FLSs, and the presence of specific caspase 3 or pan-caspase inhibitors did not affect celecoxib-induced cell death. Moreover, we could not detect other signs of apoptosis, such as cleavage of poly(ADP-ribose) polymerase, caspase 8 or 9, or DNA fragmentation. We therefore conclude that apoptosis is not the major death pathway in celecoxib-treated RA FLSs.