Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-α in endothelial cells
Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-α in endothelial cells
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DOI：
10.1161/01.atv.0000106321.63667.24
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发表时间：
2004-01-01
影响因子：
8.7
通讯作者：
Chien, S
中科院分区：
文献类型：
--
作者：
Chiu, JJ;Lee, PL;Chien, S
目的-血管内皮细胞（EC）受到剪切应力和细胞因子刺激。我们研究了剪切应力和细胞因子在调节 EC 中粘附分子基因表达方面的相互作用。方法和结果-在添加肿瘤坏死因子 (TNF)-α 之前和/或之后对 EC 施加剪切应力 (20 达因/厘米 (2))。剪切应力增加了 TNF-α 诱导的细胞间粘附分子 1 (ICAM-1) 在 mRNA 和表面蛋白水平的表达，但降低了 TNF-α 诱导的血管粘附分子 1 (VCAM-1) 和 E-选择素的表达。使用 ICAM-1、VCAM-1 和 E-选择素的启动子报告基因构建体进行的转染研究表明，这些基因表达的剪切应力调节发生在转录水平。经过 24 小时预剪切和 1 小时静态孵育后，预剪切对 TNF-α 诱导的 ICAM-1 mRNA 表达的影响消失了。然而，预剪切后 TNF-α 诱导的 VCAM-1 和 E-选择素 mRNA 表达的恢复需要 > 6 小时的静态孵育时间（24 小时完全恢复）。剪切前和剪切后导致 EC 细胞核中 TNF-α 诱导的核因子-kappaB-DNA 结合活性降低。结论 - 我们的研究结果表明，剪切应力在调节 TNF-α 诱导的 EC 中 ICAM-1 与 VCAM-1 和 E-选择素基因的表达方面发挥着不同的作用。
Objective-Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes in ECs.Methods and Results-Shear stress (20 dynes/cm(2)) was applied to ECs prior to and/or following the addition of tumor necrosis factor (TNF)-alpha. Shear stress increased the TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-alpha-induced expression of vascular adhesion molecule-1 (VCAM-1) and E-selectin. Transfection studies using promoter reporter gene constructs of ICAM-1, VCAM-1, and E-selectin demonstrated that these shear stress modulations of gene expression occur at the transcriptional levels. After 24-hour preshearing followed by 1 hour of static incubation, the effect of preshearing on TNF-alpha-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-alpha-induced VCAM-1 and E-selectin mRNA expressions following preshearing, however, required a static incubation time of >6 hours (complete recovery at 24 hours). Pre- and postshearing caused a reduction in the nuclear factor-kappaB-DNA binding activity induced by TNF-alpha in the EC nucleus.Conclusions-Our findings suggest that shear stress plays differential roles in modulating the TNF-alpha-induced expressions of ICAM-1 versus VCAM-1 and E-selectin genes in ECs.