Endothelin-1 and monocyte chemoattractant protein-1 modulation in ischemia and human brain-derived endothelial cell cultures
Endothelin-1 and monocyte chemoattractant protein-1 modulation in ischemia and human brain-derived endothelial cell cultures
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DOI：
10.1016/s0165-5728(01)00280-6
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发表时间：
2001-05-01
影响因子：
3.3
通讯作者：
Hofman, FM
中科院分区：
文献类型：
--
作者：
Chen, P;Shibata, M;Hofman, FM
已经显示，由缺血/再灌注引起的脑组织损伤部分是由活化的巨噬细胞浸润到缺血后的脑中引起的。使用大脑中动脉闭塞（MCAO）小鼠模型，这项研究表明，在体内，浴内皮素-1（Et-1），一种有效的血管收缩剂，和巨噬细胞趋化因子，单核细胞趋化因子-1（MCP-1）诱导缺血。进一步的研究表明，在体外，Et-1可以直接刺激MCP-1 mRNA和MCP-1蛋白的表达，并且这种Et-1诱导的MCP-1的产生是由ETA受体介导的。炎性细胞因子，肿瘤坏死因子α和白细胞介素-1 β，分别与Et-1相加和协同作用，以增加MCP-1的产生。Et-1诱导MCP-1产生的信号转导途径的部分阐明表明，蛋白激酶C-，但不cAMP依赖的途径参与。这些数据表明，Et-1作为一种炎症肽，增加MCP-1的水平，表明在缺血/再灌注损伤过程中的趋化因子调节机制。(C)出版社：Elsevier Science B. V.
Brain tissue damage due to ischemia/reperfusion has been shown to be caused, in part, by activated macrophages infiltrating into the post-ischemic brain. Using the Middle Cerebral Artery Occlusion (MCAO) mouse model, this study demonstrated that, in vivo, bath endothelin-1 (Et-1), a potent vasoconstrictor, and the macrophage chemokine, monocyte chemoattractant factor-1 (MCP-1) are induced in ischemia. Further studies, using human brain-derived endothelial cells (CNS-EC), showed that in vitro, Et-1 can directly stimulate MCP-1 mRNA expression and MCP-1 protein; and this Et-1-induced MCP-1 production is mediated by the ETA receptor. Inflammatory cytokines, tumor necrosis factor alpha and interleukin-1 beta, functioned additively and synergistically, respectively, with Et-1 to increase this MCP-1 production. Partial elucidation of the signal transduction pathways involved in Et-1-induced MCP-1 production demonstrated that protein kinase C-, but not cAMP-dependent pathways are involved. These data demonstrate that Et-1 functioning as an inflammatory peptide, increased levels of MCP-1, suggesting a mechanism for chemokine regulation during ischemia/reperfusion injury. (C) 2001 Published by Elsevier Science B.V.