Oscillating flow promotes inflammation through the TLR2-TAK1-IKK2 signalling pathway in human umbilical vein endothelial cell (HUVECs)
Oscillating flow promotes inflammation through the TLR2-TAK1-IKK2 signalling pathway in human umbilical vein endothelial cell (HUVECs)
复制标题
振荡流通过人脐静脉内皮细胞 (HUVEC) 中的 TLR2-TAK1-IKK2 信号通路促进炎症
DOI：
10.1016/j.lfs.2019.03.033
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Zhang Junjie
中科院分区：
文献类型：
--
作者：
Wang Feng;Wang Zhimei;Pu Jiangqin;Xie Xiangrong;Gao Xiaofei;Gu Yue;Chen Shaoliang;Zhang Junjie
研究背景动脉粥样硬化病变区存在振荡剪切应力（Oscillatory shear stress，OSS）。Toll样受体2（TLR 2）与机械应激介导的信号通路激活相关，可能导致炎症、凋亡和动脉粥样硬化。然而，TLR 2和OSS之间联系的机制尚未完全了解。本研究旨在探讨人脐静脉内皮细胞（HUVECs）中OSS与TLR 2的关系。蛋白质表达通过蛋白质印迹和免疫荧光染色来确定。采用二氢乙锭法、RT-PCR、免疫荧光染色和蛋白质印迹法检测内皮功能。结果在体外培养条件下，OSS可激活HUVECs中TLR 2的表达。另外，OSS增加HUVECs的凋亡、炎症变化和氧化应激，这些作用通过下调TLR 2的表达而逆转。我们证明OSS通过TLR 2-TAK 1-IKK 2通路调节内皮细胞的炎症反应。在颈总动脉结扎大鼠中，在OSS处TLR 2、TAK 1和磷酸化IKK 2的表达增加，提示OSS介导的HUVECs损伤可能与TLR 2表达增加有关。因此，降低TLR 2表达或抑制TLR 2活化的策略可能是降低动脉粥样硬化发生率的有效方法。
BackgroundOscillatory shear stress (OSS) occurs in areas where atherosclerosis is prevalent. Toll-like receptor 2 (TLR2) has been associated with mechanical-stress-mediated activation of signalling pathways that may lead to inflammation, apoptosis, and atherosclerosis. Nonetheless, the mechanism underlying the connection between TLR2 and OSS is not fully understood. The purpose of this study was to investigate the link between OSS and TLR2 in human umbilical vein endothelial cell (HUVECs).MethodsMonolayer endothelial cells were stimulated or not stimulated by OSS. Protein expression was determined by western blotting and immunofluorescent staining. Endothelial function was assessed by using dihydroethidium assay, RT-PCR, immunofluorescent staining and western blotting. The carotid artery of rats was ligated for 1 week, and a section exposed to OSS was excised and analysed.ResultsIn vitro, the expression of TLR2 in HUVECs was activated by OSS. Additionally, OSS increased apoptosis, inflammatory changes, and oxidative stress in HUVECs, and these effects were reversed by down-regulation the expression of TLR2. We proved that OSS regulates the inflammatory response of endothelial cells through the TLR2–TAK1–IKK2 pathway. In the rats with carotid artery ligation, TLR2, TAK1 and phospho-IKK2 amounts increased at the site of OSS.SignificanceAccording to our results, the OSS-mediated HUVECs injury may be associated with an increase in TLR2 expression. Accordingly, strategies designed to reduce TLR2 expression or inhibit TLR2 activation may be an effective approach to reduce the incidence of atherosclerosis.