活化蛋白C通过内皮细胞蛋白C受体抑制TNF-α介导的炎症反应(英文)  

Activated Protein Cameliorates TNF-α-induced Inflammatory Response of Endothelium Via the Endothelial Protein C Receptor

作　　者：陈友琴[1,5] 彭军[2,3] 刘肖珩[4] 吴江[4] 李汝恒[5] 郑晓红[5] 

机构地区：[1]Department of Pediatrics, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevord, Oklahoma City, OK 73190, USA [2]Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543 [3]福建中医学院中西医结合研究院,福州350108 [4]四川大学华西医学中心生物医学工程研究室,成都610041 [5]大理学院物理与电子信息学院,大理671003

出　　处：《生物医学工程学杂志》2009年第3期625-630,共6页Journal of Biomedical Engineering

摘　　要：活化蛋白C(APC)在抑制炎症反应中起着重要作用,内皮细胞蛋白C受体(EPCR)可以增加蛋白C的活化。已有的研究表明:APC通过抑制细胞因子和化学趋化因子的分泌以及黏附分子的表达来调节炎症反应,但其作用机制还不完全明了。本文研究了APC对TNF-α诱导的细胞因子分泌和黏附分子表达的影响,同时探讨了其可能的作用机制。结果显示:APC能显著抑制TNF-α诱导的细胞因子分泌(IL-1α和IL-8)和黏附分子表达(ICAM-1,VCAM-1 and E-selction);抗EPCR的单克隆抗体显著拮抗了APC抑制细胞因子分泌和黏附分子表达的功能。结论:APC通过抑制炎症因子的产生来调节炎症反应,这种作用可能是通过与内皮细胞EPCR的相互作用来实现。It has been demonstrated that the activated protein C （APC） plays an important role in the inhibition of inflammation. The activation of protein C can be significantly enhanced by the endothelial cell protein C receptor （EPCR）. Previous studies proposed that the APC regulates the inflammatory response in endothelial cells by suppressing the expression of adhesion molecules and the secretion of chemokines and cytokines. However, the precise mechanism of the inhibitory effect of APC on inflammation is still poorly understood. In the present study, we evaluated the anti-inflammatory effect of recombinant human APC （rhAPC） and whether its inhibitory effect is conducted through the EPCR-dependent mechanism on human umbilical vein endothelial cells （HUVECs）. By exposing HUVECs to.. （1） TNF-α （2） rhAPC plus TNF-α （3） anti EPCR antibody that prevents rhAPC interaction with EPCR; （4） TNF-α plus anti EPCR antibody; （5） rhAPC plus TNF-α in the presence of anti EPCR antibody, we found that APC was able to significantly inhibit the TNF-α-indueed secretion of eytokines such as IL-1β and IL-8, as well as the expression of adhesion molecules such as ICAM-1, VCAM-1 and E-selction in HUVECs. These results reveal a novel pathway by which APC protects endothelial cells from inflammatory mediators through an EPCR-dependent mechanism.

关 键 词：活化蛋白C 内皮细胞蛋白C受体 细胞因子 黏附分子 

分 类 号：R363[医药卫生—病理学]