Activation of human umbilical vein endothelial cells leads to relocation and release of high-mobility group box chromosomal protein 1
Activation of human umbilical vein endothelial cells leads to relocation and release of high-mobility group box chromosomal protein 1
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DOI：
10.1111/j.0300-9475.2004.01518.x
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发表时间：
2004-12-01
影响因子：
3.7
通讯作者：
Treutiger, CJ
中科院分区：
文献类型：
--
作者：
Mullins, GE;Sunden-Cullberg, J;Treutiger, CJ
核蛋白高迁移率族蛋白1（HMGB 1）最近被描述为一种促炎细胞因子，并作为严重脓毒症和脓毒性休克的晚期介质。该蛋白响应内毒素从单核细胞释放，并通过核因子κ B激活单核细胞和内皮细胞。我们以前已经证明，HMGB 1的B盒介导的促炎症作用的内皮细胞，包括细胞粘附分子的上调和白细胞介素（IL）-8和粒细胞集落刺激因子的释放。在这里，我们报告说，HMGB 1释放从人脐静脉内皮细胞（HUVEC）响应脂多糖（LPS）和肿瘤坏死因子（TNF）-α。HMGB 1在4 h时出现核定位至胞浆。随后，在刺激16 h后的细胞上清液中可以看到大量的HMGB 1。还观察到HMGB 1的促炎活性对地塞米松敏感。有趣的是，HMGB 1诱导的单核细胞TNF-α释放可以被蛋白质的A-box或p38抑制剂CNI-1493抑制，但对HUVEC上细胞粘附分子的HMGB 1依赖性上调没有任何抑制作用。总之，这些结果表明，HUVEC可能是一个重要的来源，HMGB 1分泌系统性感染的反应，内皮细胞和单核细胞可能使用不同的信号通路。
The nuclear protein high-mobility group box chromosomal protein 1 (HMGB1) was recently described to act as a pro-inflammatory cytokine and as a late mediator of severe sepsis and septic shock. The protein is released from monocytes in response to endotoxin and activates monocytes and endothelial cells through nuclear factor kappa B. We have previously demonstrated that the B-box of HMGB1 mediates a pro-inflammatory effect on endothelial cells including the upregulation of cell-adhesion molecules and release of interleukin (IL)-8 and granulocyte colony-stimulating factor. Here, we report that HMGB1 is released from human umbilical vein endothelial cells (HUVEC) in response to lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-alpha. A nuclear relocation of HMGB1 to the cytoplasm was seen at 4 h. Subsequently, high amounts of HMGB1 could be seen in the supernatants from stimulated cells after 16 h. It was also observed that the pro-inflammatory activity of HMGB 1 is sensitive to dexamethasone. Interestingly, the HMGB1-induced TNF-alpha release from monocytes could be inhibited by either the A-box of the protein or the p38 inhibitor CNI-1493, but neither had any inhibitory effects on the HMGB1-dependent upregulation of cell-adhesion molecules on HUVEC. Altogether, these results suggest that HUVEC may be an important source of HMGB1 secretion in response to systemic infection and that endothelial cells and monocytes may use different signalling pathways.