Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. COX-2 expression was detected in splenic T cells from 6 month-old male BXSB mice (murine lupus T cells) but not in T cells from 2 month-old male or 6-month-old female BXSB or in 6-month-old male C57BL/6 mice, indicating a strong correlation between COX-2 expression in T cells and lupus manifestation in mice. Celecoxib treatment induced apoptosis of murine lupus T cells in vitro, which was inhibited by z-VAD-fmk, a pan-caspase inhibitor. In the murine lupus T cells treated with celecoxib, procaspases 3 and 9, but not procaspase 8, were activated. In addition, celecoxib treatment decreased the mitochondrial membrane potential of murine lupus T cells. 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.
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PMID:Apoptosis of murine lupus T cells induced by the selective cyclooxygenase-2 inhibitor celecoxib: molecular mechanisms and therapeutic potential. 1776 45