期刊
FASEB JOURNAL
卷 20, 期 7, 页码 1000-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.05-4585fje
关键词
cytokines; transcription factors; smooth muscle; airway; glucocorticoid
资金
- NHLBI NIH HHS [HL057498, R01 HL057498, HL55301, R01 HL055301] Funding Source: Medline
- NIDA NIH HHS [DA11806, P50 DA011806] Funding Source: Medline
The transmembrane glycoprotein CD38 catalyzes the synthesis of the calcium mobilizing molecule cyclic ADP-ribose from NAD. In human airway smooth muscle (HASM) cells, the expression and function of CD38 are augmented by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), leading to increased intracellular calcium response to agonists. A glucocorticoid response element in the CD38 gene has been computationally described, providing evidence for transcriptional regulation of its expression. In the present study, we investigated the effects of dexamethasone, a glucocorticoid, on CD38 expression and ADP-ribosyl cyclase activity in HASM cells stimulated with TNF-alpha. In HASM cells, TNF-alpha augmented CD38 expression and ADP-ribosyl cyclase activity, which were attenuated by dexamethasone. TNF-alpha increased NF-kappa B expression and its activation, and dexamethasone partially reversed these effects. TNF-alpha increased the expression of I kappa B alpha, and dexamethasone increased it further. An inhibitor of NF-kappa B activation or transfection of cells with I kappa B mutants decreased TNF-alpha-induced CD38 expression. The results indicate that TNF-alpha-induced CD38 expression involves NF-kappa B expression and its activation and dexamethasone inhibits CD38 expression through NF-kappa B-dependent and -independent mechanisms.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据