International immunopharmacology
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Int. Immunopharmacol. · Nov 2007
Apoptosis of murine lupus T cells induced by the selective cyclooxygenase-2 inhibitor celecoxib: molecular mechanisms and therapeutic potential.
Upregulation of cyclooxygenase (COX)-2 in T cells from patients with systemic lupus erythematosus (SLE) is associated with their resistance to functional inactivation (anergy) and to activation-induced cell death through apoptosis. It has been demonstrated that celecoxib, a selective COX-2 inhibitor, can enhance apoptosis of human lupus T cells. The present study was undertaken to investigate whether COX-2 expression is also upregulated in T cells from the lupus-prone BXBS strain of mice and if murine lupus is modified by celecoxib. ⋯ These data combine to suggest that celecoxib mainly uses the mitochondrial pathway rather than FADD pathway to trigger apoptosis of COX-2 expressing murine lupus T cells. Intragastric administration of celecoxib (40 mg/kg/day for 60 days) in 6-month-old male BXSB mice effectively limited the production of serum antibodies against dsDNA. Our data suggest that celecoxib may have a beneficial effect in treating autoimmune diseases such as SLE through inducing apoptosis of autoreactive T cells.