The Role Of Ezrin In IL-13-mediated Bronchial Epithelial Damage In Asthma

Background:The damage of bronchial epithelial cells(BECs)may exist in patients with bronchial asthma(asthma).Ezrin,a membrane-cytoskeleton protein mainly derived from epithelial cells,is related to maintaining cellular morphology and intercellular adhesion and protecting barrier function of intestinal epithelial cells.Research has found that interleukin(IL)-13 may down-regulate Ezrin in BECs.Objective:To study the correlation between the level of Ezrin and the severity of asthma,and the role of Ezrin in the injury of bronchial epithelial cells.Methods:The effect of Ezrin knockdown using shRNA and signal pathway inhibitors in IL-13-stimulated 16HBE cells was studied.Ezrin levels in lavage fluid(HALF)from the mouse model of asthma were also determined by ELISA.Lung tissue expression was detected by immunohistochemistry.The level of Ezrin was measured in exhaled breath condensate(EBC)and serum in 62 asthmatics and 23 healthy subjects.Results:(1)IL-13 down-regulated ezrin expression inl6-HBE cells by 47.56%(p=0.003),partly via the STAT6 pathway,however the effect was significantly attenuated by the STAT6 inhibitor Ruxolitinib.(2)Ezrin expression was decreased in lung tissue,particularly BECs and in BALF(1.099±0.1661VS 0.3049±0.06293ng/ml)of sensitized and challenged mice.IL-13 levels were negatively correlated with ezrin expression(r＝-0.6374,p=0.0323)in murine BALF.(3)Ezrin levels in asthmatic patients were decreased in EBC(0.3538±0.03797 VS 0.1593±0.01021 ng/ml,p<0.001)and serum(0.7007±0.05559 VS 0.2792±0.02583 ng/ml,p<0.001)compared to normal subjects.Levels were much lower in poorly-controlled patients {uncontrolled subjects(EBC:0.01239 ng/ml;serum:0.03554ng/ml)and partly controlled(EBC:0.09813±0.008382 ng/ml;serum:0.1745±0.01673 ng/ml)} compared to well-controlled subjects(EBC:0.1336±0.009081ng/ml;serum:0.2563±0.0323 5ng/ml).The cutoff values in EBC and serum were respectively 0.1668ng/ml(sensitivity:95%,specificity:87.5%)and 0.2464ng/ml(sensitivity:70.27%,specificity:94.74%).EBC and serum Ezrin levels of asthma patients were correlated with lung function in asthma patients(FEV1,FEV1%pred,FVC and FEV1/FVC).Serum ezrin levels of asthmatics were negatively correlated with serum IL-13(r=-0.7458,p<0.0001)and periostin(r＝-0.6509,p<0.0001)levels.Conclusions:Our results suggested that Ezrin was down-regulated by IL-13/STAT6 pathway and might be a potential biomarker of asthma control.