Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-κB and p38 mitogen-activated protein kinase signaling pathways
Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-κB and p38 mitogen-activated protein kinase signaling pathways
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DOI：
10.1128/iai.69.3.1273-1279.2001
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发表时间：
2001-03-01
影响因子：
3.1
通讯作者：
Ferrante, A
中科院分区：
文献类型：
--
作者：
Jersmann, HPA;Hii, CST;Ferrante, A
细菌感染与心血管事件之间公认的关联之一是内皮细胞的激活和粘附分子的上调。细菌脂多糖（LPS）和肿瘤坏死因子α（TNF）这两种与心血管事件的病因有关的主要促炎介质被发现可以协同增强内皮细胞的粘附特性。通过流式细胞术分析和酶联免疫吸附测定确定，这些导致人脐静脉内皮细胞中细胞间粘附分子-1、E-选择素和血管细胞粘附分子-1的协同上调。这种协同作用并不是由于 TNF 导致 CD14 表达上调。 LPS 和 TNF 联合治疗导致 NF-KB 转入细胞核的情况显着增加。 p38丝裂原激活蛋白激酶的活性也协同增强，而c-jun N末端激酶的活性以累加的方式增加。结果表明，LPS 和 TNF 协同作用，上调内皮细胞粘附分子的表达，可能是通过放大转录上游的信号通路来实现的。这些发现对于理解革兰氏阴性菌低度感染中动脉粥样硬化事件的加速具有重要意义。
One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-KB into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.