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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappaB pathway activation.
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Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappaB pathway activation.

机译:肿瘤坏死因子样凋亡的弱诱导剂通过核因子-κB途径的激活增加神经血管单位的通透性。

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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily. TWEAK acts on responsive cells via binding to a small cell-surface receptor named fibroblast growth factor-inducible-14 (Fn14). TWEAK can stimulate numerous cellular responses including cell proliferation, migration, and proinflammatory molecule production. The present study investigated whether TWEAK plays a role in the regulation of the permeability of the neurovascular unit (NVU). We found that intracerebral injection of TWEAK in wild-type mice induces activation of the nuclear factor-kappaB (NF-kappaB) pathway and matrix metalloproteinase-9 (MMP-9) expression in the brain with resultant disruption in the structure of the NVU and increase in the permeability of the blood-brain barrier (BBB). TWEAK did not increase MMP-9 activity or BBB permeability when injected into mice genetically deficient in the NF-kappaB family member p50. Furthermore, we report that inhibition of TWEAK activity during cerebral ischemia with an Fn14-Fc decoy receptor results in significant preservation of the integrity of the NVU with attenuation of cerebral ischemia-induced increase in the permeability of the BBB. We conclude that the cytokine TWEAK plays a role in the disruption of the structure and permeability of the NVU during physiological and pathological conditions.
机译:肿瘤坏死因子样凋亡的弱诱导物(TWEAK)是肿瘤坏死因子超家族的成员。 TWEAK通过与称为成纤维细胞生长因子诱导型14(Fn14)的小细胞表面受体结合而作用于反应性细胞。 TWEAK可以刺激多种细胞反应,包括细胞增殖,迁移和促炎分子产生。本研究调查了TWEAK是否在调节神经血管单位(NVU)的通透性中起作用。我们发现,在野生型小鼠中脑内注射TWEAK会诱导脑中核因子-κB(NF-kappaB)途径和基质金属蛋白酶9(MMP-9)表达的激活,从而导致NVU和增加血脑屏障(BBB)的渗透性。当将TWEAK注射到遗传上缺乏NF-κB家族成员p50的小鼠体内时,它不会增加MMP-9活性或BBB通透性。此外,我们报告说,用Fn14-Fc诱饵受体抑制脑缺血期间的TWEAK活性可显着保留NVU的完整性,并减弱脑缺血引起的BBB通透性增加。我们得出的结论是,在生理和病理条件下,细胞因子TWEAK在NVU的结构和通透性破坏中起作用。

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