title: TSLP signaling blocking alleviates E-cadherin dysfunction of airway epithelium in a HDM-induced asthma model.
abstract: Recent studies have indicated that Thymic stromal lymphopoietin (TSLP) plays an important role in the prevention and treatment of asthma. However the role of TSLP in dysfunction of airway epithelial adherens junctions E-cadherin in house dust mite (HDM)-induced asthma has not been addressed. We hypothesized that TSLP contributed to HDM-induced E-cadherin dysfunction in asthmatic BALB/c mice and 16HBE cells. In vivo, a HDM-induced asthma mouse model was set up for 8weeks. Mice inhaled an anti-TSLP monoclonal antibody (mAb) before HDM. The mice treated with the anti-TSLP mAb ameliorated airway inflammation, the decreasing and aberrant distribution of E-cadherin and β-catenin as well as phosphorylation(p)-AKT induced by HDM. In vitro, HDM increased the expression of TSLP and E-cadherin dysfunction by PI3K/Akt signaling pathway. The exposure of 16HBE to TSLP resulted in redistribution of E-cadherin. These results indicate that TSLP may be an important contributor in E-cadherin dysfunction of HDM-induced asthma. TSLP signaling blocking shows a protective effect in mice and that the PI3K/Akt pathway may play a role in this process.
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: 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: 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: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Yu
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: Haijin
authors.initials: H
authors.lastname: Zhao
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: 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. Electronic address: caishaox@fimmu.com.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D001980:Bronchi / Q000166:cytology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D039981:Pyroglyphidae / Q000276:immunology*; D011897:Random Allocation; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D051176:beta Catenin / Q000032:analysis; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000911:Antibodies, Monoclonal; C495270:CTNNB1 protein, human; D015820:Cadherins; D002867:Chromones; D016207:Cytokines; D009025:Morpholines; D051176:beta Catenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D000094632:Thymic Stromal Lymphopoietin
keywords: Airway epithelium; Asthma; E-cadherin; House dust mite; PI3K/Akt pathway; TSLP