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首页> 外文期刊>International immunopharmacology >Necroptosis in pulmonary macrophages mediates lipopolysaccharide-induced lung inflammatory injury by activating ZBP-1
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Necroptosis in pulmonary macrophages mediates lipopolysaccharide-induced lung inflammatory injury by activating ZBP-1

机译：肺巨噬细胞中的坏死通过激活ZBP-1介导脂多糖诱导的肺炎损伤

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摘要

Z-DNA combined protein-1 (ZBP-1), an important necroptosis regulator, activates necrosis-associated inflammation and immune response. Increased ZBP-1 expression in necroptosis-associated inflammation correlates with activation of receptor interacting protein kinase (RIPK1)/RIPK3 and nuclear factor (NF)-築. Here we explored the role of ZBP-1-mediated necroptosis in lipopolysaccharide (LPS)-induced lung injury. Bone marrow-derived macrophages (BMDMs) transfected with a small interfering RNA against ZBP-1 or scrambled control RNA were administered to mice that had been depleted of alveolar macrophages (AMs). Then the animals were treated with E. coli LPS (2.0/mg/kg) or phosphate-buffered saline by intratracheal instillation for 48/h. LPS-induced lung inflammatory injury was verified, and the mRNA and protein expression of ZBP-1, RIPK1/RIPK3 and NF-築 in AMs were then assessed by Western blot and real time-quantitative polymerase chain reaction. In mechanistic studies in vitro, BMDM cultures were treated with different concentrations of LPS for 24/h, and the expression of ZBP-1, RIPK1/RIPK3 and NF-築 were assessed. LPS activated ZBP-1-mediated necroptosis, primarily in AMs. This activation and associated lung inflammatory injury were much weaker after AMs depletion or silencing of ZBP-1 in BMDMs, which correlated with down-regulation of RIPK1/RIPK3. These in vivo findings were confirmed in experiments with cultures of BMDMs. In conclusion, LPS induces lung inflammation and injury by activating ZBP-1-mediated necroptosis and release of pro-inflammatory cytokines by macrophages.
机译：Z-DNA组合蛋白-1（ZBP-1），一种重要的虐疮调节剂，激活坏死相关的炎症和免疫应答。增加抗体相关炎症中的ZBP-1表达与受体相互作用蛋白激酶（RIPK1）/ ripk3和核因子（NF） - Ⅳ的活化相关。在这里，我们探讨了ZBP-1介导的抗病症在脂多糖（LPS）诱导的肺损伤中的作用。将用小干扰RNA转染对ZBP-1或加扰对照RNA转染的骨髓衍生的巨噬细胞（BMDMS）施用于已经耗尽的肺泡巨噬细胞（AMS）的小鼠。然后通过脑内滴注物用大肠杆菌LPS（2.0 / mg / kg）或磷酸盐缓冲盐来处理48 / h的动物。通过Western印迹和实时定量聚合酶链反应评估，验证了LPS诱导的肺炎损伤，ZBP-1，RIPK1 / RIPK3和NF-β的mRNA和蛋白表达。在体外机械研究中，用不同浓度的LPS处理BMDM培养物24 / h，并评估ZBP-1，RIPK1 / RIPK3和NF-α的表达。 LPS激活ZBP-1介导的粪便，主要是在AMS。在BMDMS中ZBP-1的耗尽或沉默后，这种激活和相关的肺炎损伤在ZBP-1的沉默后较弱，这与RIPK1 / RIPK3的下调相关。这些在体内发现中的实验证实了BMDMS的培养物。总之，通过巨噬细胞激活Zbp-1介导的死亡和释放促炎细胞因子来诱导肺炎和损伤。

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