三氧化二砷抑制血管平滑肌细胞及单核细胞肿瘤坏死因子-α 启动子活性

三氧化二砷抑制血管平滑肌细胞及单核细胞肿瘤坏死因子-α 启动子活性

张卓琦^*, 曹希传, 黄永麟

1.徐州医学院附属医院心内科, 江苏徐州 221002;
2.中国矿业大学材料学院, 江苏徐州221009;
3.哈尔滨医科大学第一临床医学院心内科, 黑龙江哈尔滨 150001

收稿日期:2006-12-19 修回日期:2007-05-10 出版日期:2007-06-15 发布日期:2007-06-15
通讯作者: 张卓琦*

Arsenic trioxide inhibites transgenic tumor necrosis factor-α promoter activity in vascular smooth muscle cells and THP-1 monocytes in vitro

Zhuo-Qi Zhang^*, Xi-Chuan Cao, Yong-Lin Huang

1. Department of Cardiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China;
2. School of Materials Science and Engineering, China University of Mining and Technology, Xuzhou 221009, China;
3. Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China

Received:2006-12-19 Revised:2007-05-10 Online:2007-06-15 Published:2007-06-15
Contact: Zhuo-Qi Zhang*

摘要/Abstract

摘要：

目的探讨三氧化二砷 (As2O3) 对血管平滑肌细胞 (VSMCs) 及THP-1单核细胞体外转染的TNF-α基因启动子活性的调控作用。方法利用虫荧光素酶 (luciferase) 报告基因系统，构建含有人类TNF-α基因启动子的质粒DNA，经阳离子脂质体转染体外培养的VSMCs及THP-1，以LPS及Ang II刺激并经不同浓度的As2O3处理后，通过检测luciferase的活性来观察启动子活性的变化。结果本实验发现：TNF-α启动子在VSMCs及THP-1 中可高效稳定地表达，分别为阳性对照 (CMV启动子) 的58.3%和80.9%；而经LPS及Ang II刺激的VSMCs和THP-1中，TNF-α启动子活性呈现明显上调(P<0.05)。VSMCs中2 – 8 μmol·L^–1、THP-1中1 – 4 μmol·L^–1的As2O3对未受诱导的TNF-α启动子有抑制作用，更可显著抑制经LPS及Ang II刺激后上调表达的TNF-α启动子活性，并呈剂量依赖关系(P<0.05)。结论以上结果提示，As2O3对 TNF-α启动子转录活性的抑制，提示其对促炎细胞因子在转录水平的潜在抑制作用及心血管系统中的潜在抗炎作用。

关键词: 三氧化二砷, 三氧化二砷, 三氧化二砷, 肿瘤坏死因子-α 启动子, 肿瘤坏死因子-α 启动子, 肿瘤坏死因子-α 启动子, 炎症反应, 炎症反应, 炎症反应, 血管平滑肌细胞, 血管平滑肌细胞, 血管平滑肌细胞, 单核细胞, 单核细胞, 单核细胞

Abstract: Aim This study was to evaluate the effect of arsenic trioxide (As2O3) on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells (VSMCs) and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang II stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter (58.3% and 80.9%, respectively). Both LPS and Ang II significantly up-regulated TNF-α promoter activity (P<0.05). 2. As2O3 significantly inhibited, both intact and LPS/Ang II stimulated promoter activity, in a dose dependent manner (P<0.05), and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.

Key words: Arsenic trioxide, Arsenic trioxide, TNF-α promoter, TNF-α promoter, Inflammation, Inflammation, Smooth muscle cells, Smooth muscle cells, Vascular, Vascular, Monocytes, Monocytes

中图分类号:

R965

Supporting: Foundation item: National Natural Science Foundation of China (No. 30170368)
^*Corresponding author. Tel.: 86-516-85802021; fax: 86-516-85802252

张卓琦^*, 曹希传, 黄永麟

三氧化二砷抑制血管平滑肌细胞及单核细胞肿瘤坏死因子-α 启动子活性

[J]. .

Zhuo-Qi Zhang^*, Xi-Chuan Cao, Yong-Lin Huang. Arsenic trioxide inhibites transgenic tumor necrosis factor-α promoter activity in vascular smooth muscle cells and THP-1 monocytes in vitro[J]. .

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