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学科主题: 基础医学
题名:
Apoptosis of murine lupus T cells induced by the selective cvclooxygenase-2 inhibitor celecoxib: Molecular mechanisms and therapeutic potential
作者: Yang, Peng; Zhang, Yan; Ping, Lv; Gao, Xiao-Ming
关键词: COX-2 ; celecoxib ; apoptosis ; lupus ; T cells
刊名: INTERNATIONAL IMMUNOPHARMACOLOGY
发表日期: 2007-11-01
DOI: 10.1016/j.intimp.2007.06.013
卷: 7, 期:11, 页:1414-1421
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Pharmacology & Pharmacy
研究领域[WOS]: Immunology ; Pharmacology & Pharmacy
关键词[WOS]: BXSB MICE ; CYCLOOXYGENASE-2 INHIBITORS ; CHOLANGIOCARCINOMA CELLS ; ANTIINFLAMMATORY DRUGS ; DEATH ; ERYTHEMATOSUS ; ACTIVATION ; RECEPTOR ; COX-2 ; ADENOCARCINOMA
英文摘要:

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 mate 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 C5713L/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. (c) 2007 Published by Elsevier B.V

语种: 英语
WOS记录号: WOS:000249845500003
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66963
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Minist Publ Hlth, Key Lab Immunol, Beijing, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Immunol, Beijing 100083, Peoples R China

Recommended Citation:
Yang, Peng,Zhang, Yan,Ping, Lv,et al. Apoptosis of murine lupus T cells induced by the selective cvclooxygenase-2 inhibitor celecoxib: Molecular mechanisms and therapeutic potential[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2007,7(11):1414-1421.
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