TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model
TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model
复制标题
TSLP 信号传导阻断可减轻 HDM 诱导的哮喘模型中气道上皮的 E-钙粘蛋白功能障碍
DOI：
10.1016/j.cellimm.2017.02.003
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发表时间：
2017-05-01
影响因子：
4.3
通讯作者：
Cai, Shaoxi
中科院分区：
文献类型：
--
作者：
Hu, Yahui;Dong, Hangming;Cai, Shaoxi
最近的研究表明，胸腺基质淋巴细胞生成素（TSLP）在哮喘的预防和治疗中发挥着重要作用。然而，TSLP 在屋尘螨 (HDM) 诱发的哮喘中气道上皮粘附连接 E-钙粘蛋白功能障碍中的作用尚未得到解决。我们假设 TSLP 导致哮喘 BALB/c 小鼠和 16HBE 细胞中 HDM 诱导的 E-钙粘蛋白功能障碍。在体内，建立HDM诱导的哮喘小鼠模型8周。小鼠在 HDM 之前吸入抗 TSLP 单克隆抗体 (mAb)。用抗 TSLP mAb 治疗的小鼠改善了气道炎症、E-钙粘蛋白和 β-连环蛋白的减少和异常分布以及 HDM 诱导的磷酸化 (p)-AKT。在体外，HDM 通过 PI3K/Akt 信号通路增加 TSLP 的表达和 E-cadherin 功能障碍。 16HBE 暴露于 TSLP 导致 E-钙粘蛋白重新分布。这些结果表明 TSLP 可能是 HDM 诱导的哮喘 E-钙粘蛋白功能障碍的重要贡献者。 TSLP 信号传导阻断在小鼠中显示出保护作用，并且 PI3K/Akt 通路可能在此过程中发挥作用。 (C) 2017 年，爱思唯尔公司出版
Recent studies have indicated that Thymic stromal lymphopoietin ( TSLP) plays an important role in the prevention and treatment of asthma. However the role of TSLP in dysfunction of airway epithelial adherens junctions E-cadherin in house dust mite (HDM)-induced asthma has not been addressed. We hypothesized that TSLP contributed to HDM-induced E-cadherin dysfunction in asthmatic BALB/c mice and 16HBE cells. In vivo, a HDM-induced asthma mouse model was set up for 8 weeks. Mice inhaled an anti-TSLP monoclonal antibody (mAb) before HDM. The mice treated with the anti-TSLP mAb ameliorated airway inflammation, the decreasing and aberrant distribution of E-cadherin and beta-catenin as well as phosphorylation(p)-AKT induced by HDM. In vitro, HDM increased the expression of TSLP and E-cadherin dysfunction by PI3K/Akt signaling pathway. The exposure of 16HBE to TSLP resulted in redistribution of E-cadherin. These results indicate that TSLP may be an important contributor in E-cadherin dysfunction of HDM-induced asthma. TSLP signaling blocking shows a protective effect in mice and that the PI3K/Akt pathway may play a role in this process. (C) 2017 Published by Elsevier Inc.