C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.
C/T conversion alters interleukin-1A promoter function in a human astrocyte cell line.
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C/T 转换改变人星形胶质细胞系中白细胞介素 1A 启动子的功能。
DOI：
10.1016/j.lfs.2006.12.011
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发表时间：
2007
期刊：
影响因子：
6.1
通讯作者：
Du,Yansheng
中科院分区：
文献类型：
--
作者：
Wei,Xing;Chen,Xianming;Fontanilla,Christine;Zhao,Liming;Liang,Zhong;Dodel,Richard;Hampel,Hampel;Farlow,Martin;Du,Yansheng
最近，白细胞介素1 A基因启动子(−889，胸腺嘧啶/胸腺嘧啶(T/T))与阿尔茨海默病的关联被报道，提示该细胞因子可能在疾病的发生发展中起重要作用。为了了解白细胞介素1 A启动子在阿尔茨海默病中的作用机制，在SVG星形胶质细胞系中进行了一项比较白细胞介素1 A基因多态性启动子功能的研究。通过检测荧光素酶报告基因在SVG细胞中的转录活性，分析胸腺嘧啶和胞嘧啶对IL-1a启动子转录活性的影响。我们的结果表明，胞嘧啶/胸腺嘧啶的转换增加了SVG细胞中IL-1a启动子的活性。水杨酸钠和洛伐他汀均能阻断星形胶质细胞中诱导的启动子活性。多态(T/T)诱导的启动子活性可能导致白介素1α蛋白表达上调和细胞因子周期放大，从而促进疾病的发展。
Recently, association of an interleukin-1A promoter polymorphism (−889, thymine/thymine (T/T)) with Alzheimer's disease was reported, suggesting that this cytokine may play an important role in disease development. To understand the mechanism underlying the interleukin-1A promoter's role in Alzheimer's disease, a study comparing promoter function of an interleukin-1A polymorphism was performed in the SVG astroglia cell line. The effects of thymine and cytosine on transcriptional activity of the interleukin-1A promoter were analyzed by testing luciferase-reporter activity in transfected SVG cells. Our results demonstrate that cytosine/thymine conversion increases activity of the interleukin-1A promoter in SVG cells. Both sodium salicylate and lovastatin are able to block induced promoter activities in astroglial cells. Induced promoter activity by the polymorphism (T/T) may result in the upregulation of interleukin-1α protein and “cytokine cycle” amplification, which may promote disease development.