单位：[1]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China江苏省人民医院[2]Data Science Institute, Department of Computing, Imperial College London, London, UK[3]Airway Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK[4]Department of Allergy, Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China[5]Shandong Key Laboratory of Infections Respiratory Disease, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China[6]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China内科学系呼吸内科华中科技大学同济医学院附属同济医院
BackgroundAllergen source-derived proteases are a critical factor in the formation and development of asthma. The cysteine protease activity of house dust mite (HDM) disrupts the epithelial barrier function. The expression of cystatin SN (CST1) is elevated in asthma epithelium. CST1 inhibits the cysteine protease activity. We aimed to elucidate the role of epithelium-derived CST1 in the development of asthma caused by HDM. MethodsCST1 protein levels in sputum supernatants and serum of patients with asthma and healthy volunteers were measured by ELISA. The ability of CST1 protein to suppress HDM-induced bronchial epithelial barrier function was examined in vitro. The effects of exogenous CST1 protein on abrogating HDM-induced epithelial barrier function and inflammation were examined in mice in vivo. ResultsCST1 protein levels were higher in sputum supernatants (142.4 +/- 8.95 vs 38.87 +/- 6.85 ng/mL, P < 0.0001) and serum (1129 +/- 73.82 vs 703.1 +/- 57.02 pg/mL, P = 0.0035) in patients with asthma than in healthy subjects. The levels were significantly higher in patients with not well- and very poorly controlled asthma than those with well-controlled asthma. Sputum and serum CST1 protein levels were negatively correlated with lung function in asthma. CST1 protein levels were significantly lower in the serum of HDM-specific IgE (sIgE)-positive asthmatics than in sIgE-negative asthmatics. The HDM-induced epithelial barrier function disruption was suppressed by recombinant human CST1 protein (rhCST1) in vitro and in vivo. ConclusionOur data indicated that human CST1 protein suppresses asthma symptoms by protecting the asthmatic bronchial epithelial barrier through inhibiting allergenic protease activity. CST1 protein may serve as a potential biomarker for asthma control.
基金：
National Natural Science Foundation of China [82170040, 81870039]; Jiangsu Province Capability Improvement Project through Science, Technology and Education [CXZX202206]
第一作者单位：[1]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China[4]Department of Allergy, Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China[5]Shandong Key Laboratory of Infections Respiratory Disease, Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China[6]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[*1]Department of Allergy, Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China[*2]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[*3]Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
推荐引用方式(GB/T 7714)：
Yao Lei,Yuan Xijing,Fu Heng,et al.Epithelium-derived cystatin SN inhibits house dust mite protease activity in allergic asthma[J].ALLERGY.2023,78(6):1507-1523.doi:10.1111/all.15739.
APA：
Yao, Lei,Yuan, Xijing,Fu, Heng,Guo, Qinxing,Wu, Yunhui...&Yao, Xin.(2023).Epithelium-derived cystatin SN inhibits house dust mite protease activity in allergic asthma.ALLERGY,78,(6)
MLA：
Yao, Lei,et al."Epithelium-derived cystatin SN inhibits house dust mite protease activity in allergic asthma".ALLERGY 78..6(2023):1507-1523
医学