Induction of heme oxygenase 1 by arsenite inhibits cytokine-induced monocyte adhesion to human endothelial cells.
Induction of heme oxygenase 1 by arsenite inhibits cytokine-induced monocyte adhesion to human endothelial cells.
复制标题
亚砷酸盐诱导血红素加氧酶 1 抑制细胞因子诱导的单核细胞与人内皮细胞的粘附。
DOI：
10.1016/j.taap.2009.01.023
复制
发表时间：
2009
影响因子：
3.8
通讯作者：
Feng,Changjian
中科院分区：
文献类型：
--
作者：
Sun,Xi;Pi,Jingbo;Liu,Wenlan;Hudson,LaurieG;Liu,KeJian;Feng,Changjian
血红素加氧酶-1（HO-1）是一种氧化应激反应基因，在多种生理和外源刺激下表达上调。亚砷酸盐作为一种氧化应激因子，是人和啮齿动物细胞中HO-1的有效诱导剂。本研究探讨了亚砷酸钠诱导的HO-1在调节肿瘤坏死因子α（TNF-α）诱导的单核细胞与人脐静脉内皮细胞（HUVEC）粘附中的作用机制。亚砷酸钠预处理以时间和浓度依赖性方式上调HO-1，抑制TNF-α诱导的单核细胞与HUVEC的粘附和细胞间粘附分子1蛋白表达，分别为50%和40%。更重要的是，通过小干扰RNA敲低HO-1可以消除亚砷酸盐诱导的抑制作用。这些结果表明，诱导HO-1的亚砷酸盐抑制胡萝卜素诱导的单核细胞粘附到HUVEC抑制粘附分子的表达。这些发现建立了一个重要的机制之间的联系功能单核细胞粘附特性的HUVEC和诱导HO-1的亚砷酸盐。
Heme oxygenase-1 (HO-1) is an oxidative stress responsive gene upregulated by various physiological and exogenous stimuli. Arsenite, as an oxidative stressor, is a potent inducer of HO-1 in human and rodent cells. In this study, we investigated the mechanistic role of arsenite-induced HO-1 in modulating tumor necrosis factor α (TNF-α) induced monocyte adhesion to human umbilical vein endothelial cells (HUVEC). Arsenite pretreatment, which upregulated HO-1 in a time- and concentration-dependent manner, inhibited TNF-α-induced monocyte adhesion to HUVEC and intercellular adhesion molecule 1 protein expression by 50% and 40%, respectively. Importantly, knockdown of HO-1 by small interfering RNA abolished the arsenite-induced inhibitory effects. These results indicate that induction of HO-1 by arsenite inhibits the cytokine-induced monocyte adhesion to HUVEC by suppressing adhesion molecule expression. These findings established an important mechanistic link between the functional monocyte adhesion properties of HUVEC and the induction of HO-1 by arsenite.