Carvedilol Inhibits Expressions of Vascular Cell Adhesion Molecule-1, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant-1, and Interleukin-8 via NF-kappaB Inhibition in Human Endothelial Cells
Carvedilol Inhibits Expressions of Vascular Cell Adhesion Molecule-1, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant-1, and Interleukin-8 via NF-kappaB Inhibition in Human Endothelial Cells
复制标题
卡维地洛通过抑制人内皮细胞中的 NF-kappaB 来抑制血管细胞粘附分子 1、细胞间粘附分子 1、单核细胞趋化剂 1 和白细胞介素 8 的表达
DOI：
10.4070/kcj.2005.35.8.576
复制
发表时间：
2005
影响因子：
2.9
通讯作者：
J. Kang
中科院分区：
文献类型：
--
作者：
Yong Sook Kim;Y. Ahn;M. Hong;S. Joo;M. Jeong;Kye;I. Sohn;H. Park;Y. Hong;Ju Han Kim;Weon Kim;J. Cho;Jong Chun Park;J. Kang
背景和目的：卡维地洛是一种抗氧化剂，其心脏保护作用是通过抑制核因子-κB的激活来实现的。本研究旨在观察α-1和β-阻断剂卡维地洛对肿瘤坏死因子-α刺激的人脐静脉内皮细胞的影响。材料和方法：应用肿瘤坏死因子-α(10 ng/mL)分别与卡维地洛共同作用于脐静脉内皮细胞。用U-937单核细胞与HUVEC黏附的荧光染料DCFH-DA检测细胞内活性氧(ROS)水平。免疫细胞化学和Western blotting检测核因子-κB(NF-κB)p65转位到细胞核的激活情况。逆转录-聚合酶链式反应和酶联免疫吸附试验检测血管细胞黏附分子-1、细胞间黏附分子-1、单核细胞趋化蛋白-1和白介素8等依赖于核因子-κ-B的促炎分子的表达。用Western blotting检测bcl2和c-jun氨基末端蛋白激酶(JNK)的磷酸化。结果：肿瘤坏死因子-α作用后，细胞内核因子κB活性增强，Bcl2表达受抑，JNK2磷酸化、ROS水平升高，U-937黏附能力增强。肿瘤坏死因子α可上调血管细胞间黏附分子-1、细胞间黏附分子-1、单核细胞趋化蛋白-1和IL-8的基因和蛋白表达。卡维地洛抑制JNK的磷酸化、ROS的形成和U-937单核细胞的黏附。此外，卡维地洛通过抑制核因子-B的活化，在mRNA和蛋白水平上减少VCAM-1、ICAM-1、MCP-1和IL-8的产生。结论：卡维地洛对肿瘤坏死因子-α刺激的内皮细胞的抗炎作用可能与其清除ROS和灭活NF-κB有关。(韩流J 2005；35：576-582)
Background and Objectives：Carvedilol is an anti-oxidative, the cardioprotective effects of which are mediated by the inhibition of NF-κB activation. The present study was designed to examine the effects of carvedilol, an α1- and β-blocker, on tumor necrosis factor (TNF)-α stimulated human umbilical vein endothelial cells (HUVEC). Materials and Methods：HUVEC were treated with TNF-α (10 ng/mL) in either the absence or presence of carvedilol. The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, with the adhesion of U-937 monocyte to the HUVEC. Nuclear factor kappa B (NF-κB) activation was determined by NF-κB p65 translocation to the nucleus using Western blotting and immunocytochemistry. The expressions of NF-κB dependent pro-inflammatory molecules, i.e., vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, were measured by RT-PCR and ELISA. Bcl-2 and phosphorylation of c-Jun N-terminal protein kinase (JNK) were measured using Western blotting. Results：TNF-α treatment increased the activation of NFκB, suppressed Bcl-2, and increased the phosphorylation of JNK, the ROS level and the adhesion of U-937. The levels of mRNA and protein expressions of VCAM-1, ICAM-1, MCP-1 and IL-8 were up-regulated by TNFα. Carvedilol inhibited the phosphorylation of JNK, ROS formation and the adhesion of U-937 monocyte. In addition, carvedilol reduced the production of VCAM-1, ICAM-1, MCP-1 and IL-8 at the mRNA and protein levels, via the suppression of NF-B activation. Conclusion：These results suggested that the anti-inflammatory effects of carvedilol on TNF-α stimulated endothelial cells could be explained by its ROS-scavenging and NF-κ B inactivation properties. (Korean Circulation J 2005;35:576-582)
单核细胞中 C5a 诱导的 IL-8 基因表达需要 NF-κB 激活。
影响因子：
20.3
作者：
Hsu,MH;Wang,M;Browning,DD;Mukaida,N;Ye,RD
通讯作者：
Ye,RD