• Man Jia, Xiaoyi Yan, Xinyu Jiang, Yunhui Wu, Jiayan Xu, Yaqi Meng, Yi Yang, Xia Shan, Xiuwedi Zhang, Shan Mao, Wei Gu, Stelios Pavlidis, Peter J Barnes, Ian M Adcock, Mao Huang, and Xin Yao.
• 1 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
• Am. J. Respir. Crit. Care Med. 2019 Feb 15; 199 (4): 496507496-507.

RationaleBronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells.ObjectivesTo study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity.MethodsLevels of ezrin were measured in exhaled breath condensate (EBC) and serum in patients with asthma and BAL fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells. Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells.Measurements And Main ResultsEzrin levels were decreased in asthmatic EBC (92.7 ± 34.99 vs. 150.5 ± 10.22 pg/ml, P < 0.0001) and serum (700.7 ± 55.59 vs. 279.2 ± 25.83 pg/ml, P < 0.0001) compared with normal subjects. Levels were much lower in uncontrolled (P < 0.001) and partly controlled patients (P < 0.01) compared with well-controlled subjects. EBC and serum ezrin levels correlated with lung function in patients with asthma and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced downregulation of ezrin expression in primary bronchial epithelial cells was significantly attenuated by the Janus tyrosine kinase 2 inhibitor, TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces, and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of "asthmatic" mice and negatively correlated with BALF IL-13 level.ConclusionsEzrin downregulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control.

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