title: Regulation of Viral Infection-induced Airway Remodeling Cytokine Production by the TLR3-EGFR Signaling Pathway in Human Bronchial Epithelial Cells.
abstract: Toll-like receptor 3 (TLR3) is involved in the virus-induced pulmonary inflammatory response, but its role in airway remodeling after viral infection is unclear. We explored the role of TLR3 in poly(I:C)-induced inflammatory cytokines and mucin 5AC (MUC5AC) production in human bronchial epithelial cells by Western blotting, RT-PCR and ELISA. The expression of TLR3, MUC5AC, Matrixmetalloproteinase (MMP9), Transforming growth factor (TGF-β1) and Vascular endothelial growth factor (VEGF) in human bronchial epithelial cells increased in a dose-dependent manner after exposure to poly(I:C), and this effect was inhibited by treatment with TLR3 siRNA. The phosphorylation of epithelial growth factor receptor (EGFR)/ERK/P38 Mitogen-activated protein kinases (MAPK) proteins increased after poly(I:C) treatment, and inhibition of this signaling pathway decreased TLR3 expression and MUC5AC and TGF-β1 production in human bronchial epithelial cells. The TLR3-EGFR signaling pathway is involved in the production of airway remodeling cytokines after virus infection. Inhibiting EGFR and its signaling pathway may be a therapeutic strategy for modifying airway remodeling.
authors.affiliation: a Department of VIP , The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: b Department of Respiratory Diseases , The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Department of Respiratory Diseases , The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Tang
authors.affiliation: b Department of Respiratory Diseases , The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: b Department of Respiratory Diseases , The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhou
mesh_terms: D056151:Airway Remodeling; D000998:Antiviral Agents / Q000494:pharmacology; D001980:Bronchi; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D055271:Mucin 5AC / Q000096:biosynthesis*; D011070:Poly I-C / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D020032:Tyrphostins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014777:Virus Diseases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D005419:Flavonoids; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D053773:Transforming Growth Factor beta1; D020032:Tyrphostins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C101044:RTKI cpd; C512478:EGFR protein, human; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D011070:Poly I-C; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: EGFR; MUC5AC; TLR3; airway remodeling