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Antisense RNA to Inducible Nitric Oxide Synthase Reduces Cytokine-Mediated Brain Endothelial Cell Death

机译:反义RNA至诱导型一氧化氮合酶减少细胞因子介导的脑内皮细胞死亡

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We test whether inhibition of inducible nitric oxide synthase (iNOS) can exert a cytoprotective effect on cerebral endothelial cells upon stimulation by pro-inflammatory cytokines. Mouse brain endothelial cells were stably transfected to express an antisense RNA against iNOS driven by an endothelium-specific von Willebrand factor (vWF) promoter. Upon stimulation with tumor necrosis factor- (TNF-) plus interferon- (IFN-), antisense transfectants showed less iNOS enzymatic activity with less nitric oxide (NO) when compared to the sense control cells. Correspondingly, the antisense cells showed a reduced LDH release and less cytosolic content of oligonucleosomes. These findings establish a cell-specific antisense strategy and confirm the cytotoxic role of iNOS expression in cultured cerebral endothelial cells.
机译:我们测试是否抑制诱导型一氧化氮合酶(InOS)在促炎细胞因子刺激后可以对脑内皮细胞产生细胞保护作用。将小鼠脑内皮细胞稳定地转染,以表达由内皮特异性von Willebrand因子(VWF)启动子驱动的Inos的反义RNA。在刺激肿瘤坏死因子 - (TNF-)加干扰素(IFN-)后,与感测对照细胞相比,反义转染剂显示出较少一氧化氮(NO)的酶活性较少。相应地,反义细胞显示出降低的LDH释放和寡核苷酸的细胞溶胶含量减少。这些发现建立了细胞特异性的反义策略,并确认InOS表达在培养的脑内皮细胞中的细胞毒性作用。

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