Inhibition by Cigarette Smoke of Nuclear Factor-κB-Dependent Response to Bacteria in the Airway
Inhibition by Cigarette Smoke of Nuclear Factor-κB-Dependent Response to Bacteria in the Airway
复制标题
DOI：
10.1165/rcmb.2009-0454oc
复制
发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
Look, Dwight C.
中科院分区：
文献类型：
--
作者：
Manzel, Lori J.;Shi, Lei;Look, Dwight C.
虽然暴露于香烟烟雾的个体更容易受到呼吸道感染，但香烟烟雾对肺防御的影响尚未完全了解。基于细菌和宿主细胞之间的相互作用导致NF-κ B B调控的关键防御基因表达的观察，我们假设香烟烟雾改变NF-κ B功能。在这项研究中，原代人气管支气管上皮细胞与香烟烟雾提取物（CSE）处理，并暴露于流感嗜血杆菌，和CSE对细菌诱导的信号和基因表达的影响进行了评估。CSE抑制高浓度诱导的NF-κ B B活化和随后的气道上皮细胞对H.流感。这种NF-κ B活化的降低并不归因于细胞损失或细胞毒性。上皮细胞的谷氨酸增加降低了CSE对NF-κ B依赖性反应的影响，以及对NF-κ B上游调节因子κ B抑制剂和κ B激酶抑制剂的影响，表明活性氧的参与。这些发现与肺部感染的相关性用H.流感气道感染，其中在暴露于香烟烟雾的动物中发生NF-κ B通路活化、角质形成细胞趋化因子（KC）表达和中性粒细胞募集减少。结果表明，尽管香烟烟雾可引起肺部炎症，但暴露于烟雾中会抑制肺对H。流感，从而为暴露于香烟烟雾的个体对呼吸道细菌感染的易感性增加提供了一种解释。
Although individuals exposed to cigarette smoke are more susceptible to respiratory infection, the effects of cigarette smoke on pulmonary defense are incompletely understood. Based on the observation that interactions between bacteria and host cells result in the expression of critical defense genes regulated by NF-kappa B, we hypothesized that cigarette smoke alters NF-kappa B function. In this study, primary human tracheobronchial epithelial cells were treated with cigarette smoke extract (CSE) and exposed to Haemophilus influenzae, and the effects of CSE on bacteria-induced signaling and gene expression were assessed. CSE inhibited high concentrations of induced NF-kappa B activation and the consequent expression of defense genes that occurred in airway epithelial cells in response to H. influenzae. This decreased activation of NF-kappa B was not attributable to cell loss or cytotoxicity. Glutathione augmentation of epithelial cells decreased the effects of CSE on NF-kappa B-dependent responses, as well as the effects on the inhibitor of kappa B and the inhibitor of kappa B kinase, which are upstream NF-kappa B regulators, suggesting the involvement of reactive oxygen species. The relevance of these findings for lung infection was confirmed using a mouse model of H. influenzae airway infection, in which decreased NF-kappa B pathway activation, keratinocyte chemoattractant (KC) chemokine expression, and neutrophil recruitment occurred in animals exposed to cigarette smoke. The results indicate that although cigarette smoke can cause inflammation in the lung, exposure to smoke inhibits the robust pulmonary defense response to H. influenzae, thereby providing one explanation for the increased susceptibility to respiratory bacterial infection in individuals exposed to cigarette smoke.