TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model

TSLP 信号阻断可减轻 HDM 诱发的哮喘模型中气道上皮的 E-钙粘蛋白功能障碍

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作者:Yahui Hu, Hangming Dong, Mengchen Zou, Chaowen Huang, Lishan Luo, Changhui Yu, JiaLong Chen, Zhefan Xie, Haijin Zhao, Yanqing Le, Fei Zou, Laiyu Liu, Shaoxi Cai

Abstract

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 8weeks. 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 β-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.

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