Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.
Sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection.
复制标题
横向烟雾暴露增加了气道上皮对腺病毒感染的敏感性。
DOI：
10.1371/journal.pone.0049930
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Excoffon KJ
中科院分区：
文献类型：
--
作者：
Sharma P;Kolawole AO;Core SB;Kajon AE;Excoffon KJ
虽然重要的流行病学证据表明，香烟烟雾暴露增加病毒感染的发病率和严重程度，呼吸道对病毒病原体易感性增加背后的分子机制尚不清楚。腺病毒是一种无包膜的DNA病毒，是急性呼吸道疾病的重要病原体。柯萨奇病毒和腺病毒受体（CAR）是许多腺病毒的主要受体。我们假设香烟烟雾暴露通过增加顶端CAR的丰度来增加上皮对腺病毒感染的易感性。以培养的人气道上皮细胞（CaLu-3）为模型，研究了侧流香烟烟雾（SSS）、主流香烟烟雾（MSS）或对照空气暴露对极化的呼吸道上皮细胞对腺病毒感染的易感性的影响。使用Cultex空气-液体界面暴露系统，我们发现了SSS和MSS暴露之间上皮易感性的新差异。SSS暴露上调CAR的八外显子同种型，并增加腺病毒从顶端表面进入，而MSS暴露与对照空气暴露相似。此外，细胞糖原合成酶激酶3β（GSK 3 β）的水平通过SSS暴露下调，并且用特异性GSK 3 β抑制剂治疗重现了SSS暴露对CAR表达和病毒感染的影响。这是首次显示SSS暴露直接增强极化上皮对常见呼吸道病毒病原体感染的易感性。这项工作为SSS对呼吸道病毒感染负担的影响提供了新的理解，并可能导致改变病毒感染的新策略。此外，由于GSK 3 β抑制剂作为多种疾病的治疗剂正在进行深入的临床研究，因此这些研究可能会为扩展临床相关治疗剂的使用提供见解，并增加对潜在副作用的理解。
Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR. Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette smoke (MSS), or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control air exposure. Additionally, the level of cellular glycogen synthase kinase 3β (GSK3β) is downregulated by SSS exposure and treatment with a specific GSK3β inhibitor recapitulates the effects of SSS exposure on CAR expression and viral infection. This is the first time that SSS exposure has been shown to directly enhance the susceptibility of a polarized epithelium to infection by a common respiratory viral pathogen. This work provides a novel understanding of the impact of SSS on the burden of respiratory viral infections and may lead to new strategies to alter viral infections. Moreover, since GSK3β inhibitors are under intense clinical investigation as therapeutics for a diverse range of diseases, studies such as these might provide insight to extend the use of clinically relevant therapeutics and increase the understanding of potential side effects.