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TLR4-MyD88 signaling pathway is responsible for acute lung inflammation induced by reclaimed water.
Journal of Hazardous Materials ( IF 12.2 ) Pub Date : 2020-04-02 , DOI: 10.1016/j.jhazmat.2020.122586 Gang Liu 1 , Yun Lu 1 , Liangliang Shi 1 , Yunru Ren 1 , Jiayang Kong 1 , Mengyu Zhang 2 , Menghao Chen 1 , Wanli Liu 2
Journal of Hazardous Materials ( IF 12.2 ) Pub Date : 2020-04-02 , DOI: 10.1016/j.jhazmat.2020.122586 Gang Liu 1 , Yun Lu 1 , Liangliang Shi 1 , Yunru Ren 1 , Jiayang Kong 1 , Mengyu Zhang 2 , Menghao Chen 1 , Wanli Liu 2
Affiliation
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Previous research found that inhalation exposure of reclaimed water could cause severe pulmonary inflammation, and the endotoxin was proposed to be the key risk factor. To further support this view, the toxic effects of different reclaimed water induced by acute inhalation exposure were compared between wildtype C57BL/6J and TLR4 signaling pathway defect mice. It was found that reclaimed water with high levels of endotoxin could induce strong inflammation in wildtype mice, but not in Tlr4-/- and MyD88-/- mutants. The mixed bacterial culture from the reclaimed water showed very weak response in wildtype mice and no response in TLR4-signaling pathway deficient mice, which further suggested that the cell-bound endotoxins contribute little in the inflammation induced by reclaimed water. In addition, conditional knockout of the Tlr4 gene in myeloid cells resulted in a significant reduction of sensitivity to the reclaimed water in mutants, which indicates that myeloid cells play the most important role in the defensive immune system against the pollutants in the water. In general, this study demonstrated that the TLR4-MyD88 signaling pathway is responsible for the acute lung inflammation induced by reclaimed water, which excludes the possibility of other signaling pathway dependent inflammation inducers in reclaimed water.
中文翻译：
TLR4-MyD88信号通路负责再生水诱导的急性肺部炎症。
先前的研究发现，吸入再生水可能会导致严重的肺部炎症，而内毒素被认为是关键的危险因素。为了进一步支持该观点，在野生型C57BL / 6J和TLR4信号通路缺陷小鼠之间比较了急性吸入暴露引起的不同再生水的毒性作用。已经发现，具有高水平内毒素的再生水可以在野生型小鼠中诱导强烈的炎症，但是在Tlr4-/-和MyD88-/-突变体中则不能。来自再生水的混合细菌培养物在野生型小鼠中显示非常弱的反应，而在TLR4信号通路缺陷的小鼠中没有反应，这进一步表明，细胞结合的内毒素在再生水诱导的炎症中贡献很小。此外，髓样细胞中Tlr4基因的条件性敲除导致突变体对再生水的敏感性显着降低，这表明髓样细胞在防御水中免疫系统中起着最重要的作用。总的来说，这项研究表明，TLR4-MyD88信号通路是由再生水引起的急性肺部炎症的原因，这排除了再生水中其他依赖信号通路的炎症诱导剂的可能性。
更新日期：2020-04-21
中文翻译：
TLR4-MyD88信号通路负责再生水诱导的急性肺部炎症。
先前的研究发现，吸入再生水可能会导致严重的肺部炎症，而内毒素被认为是关键的危险因素。为了进一步支持该观点，在野生型C57BL / 6J和TLR4信号通路缺陷小鼠之间比较了急性吸入暴露引起的不同再生水的毒性作用。已经发现，具有高水平内毒素的再生水可以在野生型小鼠中诱导强烈的炎症，但是在Tlr4-/-和MyD88-/-突变体中则不能。来自再生水的混合细菌培养物在野生型小鼠中显示非常弱的反应，而在TLR4信号通路缺陷的小鼠中没有反应，这进一步表明，细胞结合的内毒素在再生水诱导的炎症中贡献很小。此外，髓样细胞中Tlr4基因的条件性敲除导致突变体对再生水的敏感性显着降低，这表明髓样细胞在防御水中免疫系统中起着最重要的作用。总的来说，这项研究表明，TLR4-MyD88信号通路是由再生水引起的急性肺部炎症的原因，这排除了再生水中其他依赖信号通路的炎症诱导剂的可能性。
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