Regulation of Viral Infection-induced Airway Remodeling Cytokine Production by the TLR3-EGFR Signaling Pathway in Human Bronchial Epithelial Cells

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-beta 1) 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-beta 1 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.