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首页> 外文期刊>American Journal of Physiology >Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin.
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Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin.

机译：呼吸道上皮细胞响应吸入的内毒素调节肺部炎症。

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摘要

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-kappa B activation in the respiratory epithelium using a mutant I kappa B-alpha construct that functioned as a dominant negative inhibitor of NF-kappa B translocation (dnI kappa B-alpha). We developed two lines of transgenic mice in which expression of dnI kappa B-alpha was targeted to the distal airway epithelium using the human surfactant apoprotein C promoter. Transgene expression was localized to the epithelium of the terminal bronchioles and alveoli. After inhalation of LPS, nuclear translocation of NF-kappa B was evident in bronchiolar epithelium of nontransgenic but not of transgenic mice. This defect was associated with impaired neutrophilic lung inflammation 4 h after LPS challenge and diminished levels of TNF-alpha, IL-1 beta, macrophage inflammatory protein-2, and KC in lung homogenates. Expression of TNF-alpha within bronchiolar epithelial cells and of VCAM-1 within peribronchiolar endothelial cells was reduced in transgenic animals. Thus targeted inhibition of NF-kappa B activation in distal airway epithelial cells impaired the inflammatory response to inhaled LPS. These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo.
机译：为了确定呼吸道上皮细胞在对吸入内毒素的炎症反应中的作用，我们使用突变的IκB-alpha构建体选择性地抑制了呼吸道上皮中的NF-κB活化，该突变体起着NF-κB易位的显性负抑制剂的作用。 （dnIκB-alpha）。我们开发了两系转基因小鼠，其中使用人类表面活性剂载脂蛋白C启动子将dnI kappa B-alpha的表达靶向远端气道上皮。转基因表达位于末端细支气管和肺泡的上皮。吸入LPS后，非转基因小鼠的细支气管上皮中有NF-κB的核易位，而转基因小鼠则没有。该缺陷与LPS攻击后4小时中性粒细胞肺炎症受损以及肺匀浆中TNF-α，IL-1β，巨噬细胞炎性蛋白2和KC水平降低有关。转基因动物中，细支气管上皮细胞内的TNF-α表达和细支气管周围内皮细胞内的VCAM-1的表达降低。因此，远端呼吸道上皮细胞中对NF-κB活化的靶向抑制削弱了对吸入LPS的炎症反应。这些数据提供了远端呼吸道上皮细胞及其传递的信号在体内肺部炎症中起生理作用的因果证据。

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