Abstract Suppression Apoptosis is not the major death mechanism induced by celecoxib on rheumatoid arthritis synovial fibroblasts

Audo, R.; Deschamps, V.; Hahne, M.; Combe, B.; Morel, J.

Arthritis Res Ther

2007 / vol 9 / pages R128


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.

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Humans; Cells, Cultured; Cell Proliferation/drug effects; Fibroblasts/drug effects/pathology; Apoptosis/drug effects; Annexin A5/metabolism; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology; Arthritis, Rheumatoid/*drug therapy/metabolism/pathology; Caspase 3/metabolism; Cell Death/drug effects; Cyclooxygenase Inhibitors/*pharmacology; Pyrazoles/*pharmacology; Staurosporine/pharmacology; Sulfonamides/*pharmacology; Synovial Membrane/*drug effects/pathology; TNF-Related Apoptosis-Inducing Ligand/pharmacology

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