High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-kappaB and Egr-1.
High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-kappaB and Egr-1.
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高迁移率组盒 1 蛋白通过激活 NF-κB 和 Egr-1 诱导血管内皮细胞组织因子表达
DOI：
10.1160/th08-11-0759
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发表时间：
2009-08
影响因子：
6.7
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Lv B;Wang H;Tang Y;Fan Z;Xiao X;Chen F
高迁移率族蛋白B1（HMGB 1）是一种丰富的核蛋白，近年来被证实是实验性脓毒症的促炎介质，虽然在动脉粥样硬化斑块中发现了细胞外HMGB 1，但其在动脉粥样硬化血栓形成中的作用尚不清楚。在本研究中，我们确定是否HMGB 1诱导组织因子（TF）在血管内皮细胞（EC）和巨噬细胞的表达。我们的数据表明，HMGB 1刺激EC表达TF（但不是TF通路抑制剂）mRNA和蛋白的浓度和时间依赖性的方式。用特异性中和抗体阻断细胞表面受体（包括TLR 4、TLR 2和TLR 4）可部分降低HMGB 1诱导的TF表达。HMGB 1还可促进内皮细胞Egr-1的表达和NF-κB（c-Rel/p65）的核转位。综上所述，我们的数据表明，HMGB 1通过细胞表面受体（TLR 4、TLR 2和TLR）以及转录因子（NF-κB和Egr-1）的激活诱导血管内皮细胞TF表达。
Summary High-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis.Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration and time-dependent manner. Blockade of cell surface receptors (including TLR4, TLR2, and RAGE) with specific neutralising antibodies partially reduced HMGB1-induced TF expression. Moreover, HMGB1 increased expression of Egr-1 and nuclear translocation of NF-κB (c-Rel/p65) in ECs. Taken together, our data suggest that HMGB1 induces TF expression in vascular endothelial cells via cell surface receptors (TLR4, TLR2, and RAGE), and through activation of transcription factors (NF-κB and Egr-1).