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.

KEYWORDS:

• TLR3
• MUC5AC
• EGFR
• airway remodeling

Funding

This work was funded by research grants from the Zhejiang Provincial Natural Science Foundation of China (no. LY15H010003) and the Major Project of the Science Technology Department of Zhejiang Province (no. 2012C13022-2).