title: LIGHT is a crucial mediator of airway remodeling.
abstract: Chronic inflammatory airway diseases like asthma and chronic obstructive pulmonary disease are major health problems globally. Airway epithelial cells play important role in airway remodeling, which is a critical process in the pathogenesis of diseases. This study aimed to demonstrate that LIGHT, an inflammatory factor secreted by T cells after allergen exposure, is responsible for promoting airway remodeling. LIGHT increased primary human bronchial epithelial cells (HBECs) undergoing epithelial-mesenchymal transition (EMT) and expressing MMP-9. The induction of EMT was associated with increased NF-κB activation and p300/NF-κB association. The interaction of NF-κB with p300 facilitated NF-κB acetylation, which in turn, was bound to the promoter of ZEB1, resulting in E-cadherin downregulation. LIGHT also stimulated HBECs to produce numerous cytokines/chemokines that could worsen airway inflammation. Furthermore, LIGHT enhanced HBECs to secrete activin A, which increased bronchial smooth muscle cell (BSMC) migration. In contrast, depletion of activin A decreased such migration. The findings suggest a new molecular determinant of LIGHT-mediated pathogenic changes in HBECs and that the LIGHT-related vicious cycle involving HBECs and BSMCs may be a potential target for the treatment of chronic inflammation airway diseases with airway remodeling.
authors.affiliation: School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Tsai
authors.forename: Inn-Wen
authors.initials: IW
authors.lastname: Chong
authors.forename: Jiunn-Min
authors.initials: JM
authors.lastname: Shieh
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
mesh_terms: D000107:Acetylation; D028341:Activins / Q000378:metabolism; D056151:Airway Remodeling; D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion; D002633:Chemotaxis; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C505914:TNFSF14 protein, human; D014157:Transcription Factors; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C422405:activin A; D028341:Activins; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D020780:Matrix Metalloproteinase 9