Cerebral microvascular IL15 is a novel mediator of TNF action.

Cerebral microvascular IL15 is a novel mediator of TNF action.
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DOI:
10.1111/j.1471-4159.2009.06371.x
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发表时间:
2009-11
影响因子:
4.7
通讯作者:
Kastin AJ
Kastin AJ
中科院分区:
医学2区
文献类型:
--
作者:
Pan W;Yu C;Hsuchou H;Khan RS;Kastin AJ

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血脑屏障(BBB)是中枢神经系统的守门人和调节界面。脑内皮细胞是血脑屏障的主要组成部分,通过产生和分泌次级物质,将炎症信号从循环调节到中枢神经系统。用RBE4脑内皮细胞芯片分析肿瘤坏死因子-α(TNF-α)诱导的炎症介质在0、6、12、2 4h的表达。白介素15(IL15)及其受体是最强烈上调的基因之一。实时定量RT-PCR和Western blotting证实了这一点。IL15受体复合体的3个亚基(IL15Rα、IL2Rβ和IL2Rγ)在表达上调的时程和幅度上表现出不同的调节作用。与特异性高亲和力受体IL15Rα表达增加一致,肿瘤坏死因子增加了细胞对125I-IL15的摄取,并增强了RBE4细胞对Alexa568-IL15的荧光强度。小鼠经肿瘤坏死因子治疗后,脑微血管中IL15受体的表达水平也增加。我们认为脑微血管IL-15系统是一种新型的炎性介质,可介导肿瘤坏死因子的作用。
The blood-brain barrier (BBB) is a gatekeeper and modulatory interface for the CNS. Cerebral endothelial cells are the major component of the BBB, and they modify inflammatory signals from the circulation to the CNS by production and secretion of secondary substances. The inflammatory mediators induced by tumor necrosis factor alpha (TNF) were determined by microarray analysis of RBE4 cerebral endothelial cells, at 0, 6, 12, or 24 h after TNF treatment. Interleukin-15 (IL15) and its receptors were among the most robustly upregulated genes. This was confirmed by real-time RT-PCR and western blotting. The three subunits of the IL15 receptor complex (IL15Rα, IL2Rβ, and IL2Rγ) showed differential regulation by TNF in their time course and amplitude of increased expression. Consistent with increased expression of the specific high affinity receptor IL15Rα, TNF increased cellular uptake of 125I-IL15 and enhanced the fluorescent intensity of Alexa568-IL15 by RBE4 cells. TNF treatment in mice also increased the level of expression of IL15 receptors in enriched cerebral microvessels. We conclude that the cerebral microvascular IL15 system is a novel inflammatory mediator that transduces the actions of TNF.
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