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: Jen-Yu Hung, Shyh-Ren Chiang, Ming-Ju Tsai, Ying-Ming Tsai, Inn-Wen Chong, Jiunn-Min Shieh, Ya-Ling Hsu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 230 Issue 5 Pg. 1042-53 (May 2015) ISSN: 1097-4652 [Electronic] United States
• PMID: 25251281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Homeodomain Proteins
• Inflammation Mediators
• NF-kappa B
• TNFSF14 protein, human
• Transcription Factors
• Tumor Necrosis Factor Ligand Superfamily Member 14
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• activin A
• Activins
• E1A-Associated p300 Protein
• EP300 protein, human
• Matrix Metalloproteinase 9

Topics

• Acetylation
• Activins (metabolism)
• Airway Remodeling
• Bronchi (cytology)
• Cell Adhesion
• Chemotaxis
• E1A-Associated p300 Protein (metabolism)
• Epithelial Cells (enzymology, metabolism)
• Epithelial-Mesenchymal Transition
• Homeodomain Proteins (metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Myocytes, Smooth Muscle (cytology)
• NF-kappa B (metabolism)
• Signal Transduction
• Transcription Factors (metabolism)
• Tumor Necrosis Factor Ligand Superfamily Member 14 (metabolism)
• Zinc Finger E-box-Binding Homeobox 1