Reduction of the expression and production of adhesion molecules and chemokines by brain endothelial cells in response to tumor necrosis factor-α and interleukin-17 in hypothermia
Reduction of the expression and production of adhesion molecules and chemokines by brain endothelial cells in response to tumor necrosis factor-α and interleukin-17 in hypothermia
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低温下脑内皮细胞对肿瘤坏死因子-α 和白细胞介素 17 的反应减少粘附分子和趋化因子的表达和产生
DOI：
10.1111/cen3.12298
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Yoshida Y
中科院分区：
文献类型：
--
作者：
Matsui T;Yoshida Y
目的黏附分子和趋化因子的上调可能促进炎性细胞在损伤脑组织中的募集和渗透，导致脑缺血后炎症反应增强，加重脑损伤。在此，我们观察了低温和高温对肿瘤坏死因子-α和白介素17诱导的脑内皮细胞表达和产生黏附分子和趋化因子的影响，以探讨其神经保护机制。方法用肿瘤坏死因子-α或白介素17在低温(33℃)、常温(37℃)和高温(39℃)条件下刺激脑内皮细胞。结果与常温相比，在肿瘤坏死因子-α刺激的BEND.3细胞中，黏附分子、细胞间黏附分子-1和血管细胞黏附分子-1的表达水平明显降低。巨噬细胞炎性蛋白-2、干扰素-γ诱导蛋白-10、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、单核细胞趋化蛋白-1、结论与常温相比，低温可直接抑制炎性细胞向中枢神经系统募集细胞黏附分子和趋化因子，从而抑制脑内皮细胞对α和IL-17刺激的反应，而高温状态可能通过直接促进α刺激的脑内皮细胞产生趋化因子而促进炎性反应。
ObjectiveThe upregulation of adhesion molecules and chemokines might facilitate the recruitment and infiltration of inflammatory cells into injured brain tissue, leading to enhanced post‐ischemic brain inflammation and exacerbated brain injury. Here we examined the effects of hypothermia and hyperthermia on the expression and production of adhesion molecules and chemokines by brain endothelial cells in response to tumor necrosis factor (TNF)‐α and interleukin (IL)‐17 in an attempt to identify the mechanisms responsible for the neuroprotection conferred by therapeutic hypothermia.MethodsBrain endothelial bEnd.3 cells were stimulated with TNF‐α or IL‐17 under hypothermia (33°C), normothermia (37°C) or hyperthermia (39°C). Levels of mRNA expression and protein production of a number of adhesion molecules and chemokines were measured.ResultsIn TNF‐α‐stimulated bEND.3 cells, the mRNA expression of adhesion molecules, intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 was reduced by hypothermia compared with normothermia. The production of chemokines, macrophage inflammatory protein‐2 (MIP‐2/CXCL2), interferon‐γ‐inducible protein‐10 (IP‐10/CXCL10) and monocyte chemoattractant protein‐1 (MCP‐1/CCL2) was reduced by hypothermia, but augmented by hyperthermia. In IL‐17‐stimulated bEND.3 cells, the mRNA expression of IP‐10/CXCL10, and the production of MIP‐2/CXCL2 and MCP‐1/CCL2 were reduced by hypothermia compared with normothermia.ConclusionsTherapeutic hypothermia might suppress the recruitment of inflammatory cells to the central nervous system by directly reducing the expression and production of cell adhesion molecules and chemokines by brain endothelial cells in response to stimulation with TNF‐α and IL‐17. Conversely, the hyperthermic state might promote such inflammatory responses by directly augmenting the TNF‐α‐stimulated brain endothelial cell production of chemokines.