title: Distinct roles of short and long thymic stromal lymphopoietin isoforms in house dust mite-induced asthmatic airway epithelial barrier disruption.
abstract: Loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Thymic stromal lymphopoietin (TSLP) may have dual immunoregulatory roles. In inflammatory disorders of the bowel, the long isoform of TSLP (lfTSLP) promotes inflammation while the short isoform (sfTSLP) inhibits inflammation. We hypothesize that lfTSLP contributes to house dust mite (HDM)-induced airway epithelial barrier dysfunction and that synthetic sfTSLP can prevent these effects. In vitro, airway epithelial barrier function was assessed by monitoring transepithelial electrical resistance, fluorescent-dextran permeability, and distribution of E-cadherin and β-catenin. In vivo, BALB/c mice were exposed to HDM by nasal inhalation for 5 consecutive days per week to establish an asthma model. sfTSLP and 1α,25-Dihydroxyvitamin D3 (1,25D3) were administered 1 h before HDM exposure. After 8 weeks, animal lung function tests and pathological staining were performed to evaluate asthma progression. We found that HDM and lfTSLP impaired barrier function. Treatment with sfTSLP and 1,25D3 prevented HDM-induced airway epithelial barrier disruption. Moreover, sfTSLP and 1,25D3 treatment ameliorated HDM-induced asthma in mice. Our data emphasize the importance of the different expression patterns and biological properties of sfTSLP and lfTSLP. Moreover, our results indicate that sfTSLP and 1,25D3 may serve as novel therapeutic agents for individualized treatment of asthma.
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Hangming
authors.initials: H
authors.lastname: Dong
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Laiyu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Mengchen
authors.initials: M
authors.lastname: Zou
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Luo
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wan
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: JiaLong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Zhefan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Le
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid; D015820:Cadherins / Q000378:metabolism; D064200:Cdh1 Proteins / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000502:physiology*; D040002:Dermatophagoides pteronyssinus; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D064200:Cdh1 Proteins; D016207:Cytokines; C577585:Fzr1 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D051176:beta Catenin; D000094632:Thymic Stromal Lymphopoietin