Background

Altered epithelial physical and functional barrier properties along with T_H1/T_H2 immune dysregulation are features of allergic asthma. Regulation of junction proteins to improve barrier function of airway epithelial cells has the potential for alleviation of allergic airway inflammation.

Objective

We sought to determine the immunomodulatory effect of knob protein of the adenoviral capsid on allergic asthma and to investigate its mechanism of action on airway epithelial junction proteins and barrier function.

Methods

Airway inflammation, including junction protein expression, was evaluated in allergen-challenged mice with and without treatment with knob. Human bronchial epithelial cells were exposed to knob, and its effects on expression of junction proteins and barrier integrity were determined.

Results

Administration of knob to allergen-challenged mice suppressed airway inflammation (eosinophilia, airway hyperresponsiveness, and IL-5 levels) and prevented allergen-induced loss of airway epithelial occludin and E-cadherin expression. Additionally, knob decreased expression of T_H2-promoting inflammatory mediators, specifically IL-33, by murine lung epithelial cells. At a cellular level, treatment of human bronchial epithelial cells with knob activated c-Jun N-terminal kinase, increased expression of occludin and E-cadherin, and enhanced epithelial barrier integrity.

Conclusion

Increased expression of junction proteins mediated by knob leading to enhanced epithelial barrier function might mitigate the allergen-induced airway inflammatory response, including asthma.

中文翻译：

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旋钮蛋白增强上皮屏障完整性并减轻气道炎症。

背景

改变的上皮物理和功能屏障特性以及 T _H 1/T _H 2 免疫失调是过敏性哮喘的特征。调节连接蛋白以改善气道上皮细胞的屏障功能具有减轻过敏性气道炎症的潜力。

客观的

我们试图确定腺病毒衣壳的旋钮蛋白对过敏性哮喘的免疫调节作用，并研究其对气道上皮连接蛋白和屏障功能的作用机制。

方法

在接受和不接受旋钮治疗的过敏原攻击小鼠中评估气道炎症，包括连接蛋白表达。将人支气管上皮细胞暴露于旋钮，并确定其对连接蛋白表达和屏障完整性的影响。

结果

向过敏原攻击的小鼠施用旋钮可抑制气道炎症（嗜酸性粒细胞增多、气道高反应性和 IL-5 水平）并防止过敏原诱导的气道上皮闭塞蛋白和 E-钙粘蛋白表达丧失。此外，旋钮降低了鼠肺上皮细胞对促进 T _H 2 的炎症介质，特别是 IL-33 的表达。在细胞水平上，用旋钮激活的 c-Jun N 末端激酶处理人支气管上皮细胞，增加了 occludin 和 E-cadherin 的表达，并增强了上皮屏障的完整性。

结论

由旋钮介导的连接蛋白表达增加导致上皮屏障功能增强，可能会减轻过敏原诱导的气道炎症反应，包括哮喘。