Distinct roles of short and long thymic stromal lymphopoietin isoforms in house dust mite-induced asthmatic airway epithelial barrier disruption
| Autor: | Changhui Yu, Mengchen Zou, Zhefan Xie, Xuan Wan, Chaowen Huang, Yanqing Le, Yahui Hu, Hangming Dong, Shaoxi Cai, Laiyu Liu, Haijin Zhao, JiaLong Chen, Lishan Luo, Fei Zou |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Thymic stromal lymphopoietin MAP Kinase Signaling System Dermatophagoides pteronyssinus Bronchi Inflammation Cdh1 Proteins Article Cell Line Pathogenesis Mice 03 medical and health sciences Thymic Stromal Lymphopoietin Antigens CD medicine Animals Humans Protein Isoforms RNA Messenger Phosphorylation beta Catenin Barrier function Asthma House dust mite Mice Inbred BALB C Multidisciplinary biology Inhalation business.industry Epithelial Cells Cadherins medicine.disease biology.organism_classification Up-Regulation respiratory tract diseases 030104 developmental biology Immunology Disease Progression Cytokines medicine.symptom business Airway Bronchoalveolar Lavage Fluid |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep39559 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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