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白细胞介素-17A通过活性氧/ p38信号通路上调肝硬化中内皮组织因子的表达。

IL-17A up-regulates expression of endothelial tissue factor in liver cirrhosis via the ROS/p38 signal pathway.

作者信息

Pu Yansong, Zhang Shu, Zhou Rui, Huang Na, Li Han, Wei Wei, Li Liang, Huang Chen, Yang Jun, Li Zongfang

机构信息

National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, Shaanxi, Xian 710004, China.

National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

出版信息

Biochem Biophys Res Commun. 2016 Jan 29;470(1):41-47. doi: 10.1016/j.bbrc.2015.12.093. Epub 2015 Dec 29.

DOI:10.1016/j.bbrc.2015.12.093
PMID:26742425
Abstract

Interleukin-17A (IL-17A), an inflammatory cytokine, is elevated in liver cirrhosis. Inflammation and coagulation dysfunction are closely related. Tissue factor (TF) is a bridge between endothelial activation, blood coagulation and inflammation. The aims of the present study were to evaluate endothelial TF expression in liver cirrhosis and identify the possible underlying role of IL-17A in TF expression. In the present study, we found that TF expression was increased on endothelium of splenic vein from cirrhotic patients and significantly correlated with intima/media ratios of splenic vein and coagulation parameters. Serum levels of IL-17A were significantly higher in cirrhotic patients as compared with normal controls. Cirrhotic serum and IL-17A stimulated TF expression in HUVECs, which was reduced by blockade of IL-17A, p38, and reactive oxygen species (ROS). Taken together, our data show that enhanced expression of endothelial TF, which plays an important role in coagulopathy and splenic vein remodeling in liver cirrhosis, is induced by IL-17A in a ROS dependent manner.

摘要

白细胞介素-17A(IL-17A)是一种炎症细胞因子,在肝硬化患者体内水平升高。炎症与凝血功能障碍密切相关。组织因子(TF)是内皮细胞活化、血液凝固和炎症之间的桥梁。本研究旨在评估肝硬化患者内皮细胞TF的表达情况,并确定IL-17A在TF表达中可能的潜在作用。在本研究中,我们发现肝硬化患者脾静脉内皮细胞上TF表达增加,且与脾静脉内膜/中膜比值及凝血参数显著相关。与正常对照组相比,肝硬化患者血清中IL-17A水平显著更高。肝硬化患者血清和IL-17A可刺激人脐静脉内皮细胞(HUVECs)中TF的表达,而通过阻断IL-17A、p38和活性氧(ROS)可使其表达降低。综上所述,我们的数据表明,IL-17A以ROS依赖的方式诱导内皮细胞TF表达增强,这在肝硬化的凝血病和脾静脉重塑中起重要作用。

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