Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo

Curtis Kuo, Sam Lim, Nicholas J C King, Nathan W Bartlett, Ross P Walton, Jie Zhu, Nicholas Glanville, Julia Aniscenko, Sebastian L Johnston, Janette K Burgess, Judith L Black, Brian G Oliver

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35 Citations (Scopus)

Abstract

BACKGROUND AND OBJECTIVE: A hallmark of asthma is airway remodelling, which includes increased deposition of extracellular matrix (ECM) protein. Viral infections may promote the development of asthma and are the most common causes of asthma exacerbations. We evaluated whether rhinovirus (RV) infection induces airway remodelling, as assessed by ECM deposition.

METHODS: Primary human bronchial epithelial cells and lung parenchymal fibroblasts were infected with RV-2 or RV-16, or treated with RV-16 RNA, imiquimod (Toll-like receptor (TLR) 7/8 agonist) or polyinosinic : polycytidylic acid (poly I : C) (activator of TLR 3, retinoic-acid-inducible protein I and melanoma-differentiated-associated gene 5). Changes in ECM proteins and their transcription were measured by ELISA and quantitative real-time PCR. In addition, gene expression for ECM proteins was assessed in a mouse model of RV infection.

RESULTS: RV infection increased deposition of the ECM protein, perlecan, by human bronchial epithelial cells, and collagen V and matrix-bound vascular endothelial growth factor were increased in both human bronchial epithelial cell and fibroblast cultures. Purified RV-16 RNA, poly I : C and imiquimod induced similar increases in ECM deposition to those observed with RV-infected fibroblasts. However, only poly I : C induced ECM deposition by bronchial epithelial cells, suggesting that RV-induced ECM deposition is mediated through TLR. Furthermore, gene expression for fibronectin and collagen I was increased in lung homogenates of mice infected with RV-1b.

CONCLUSIONS: RV infection and TLR ligands promote ECM deposition in isolated cell systems and RV induces ECM gene expression in vivo, thus demonstrating that RV has the potential to contribute to remodelling of the airways through induction of ECM deposition.

Original languageEnglish
Pages (from-to)367-77
Number of pages11
JournalRespirology
Volume16
Issue number2
DOIs
Publication statusPublished - Feb-2011

Keywords

  • Airway Remodeling
  • Aminoquinolines
  • Animals
  • Asthma
  • Bronchi
  • Cells, Cultured
  • Collagen Type V
  • Extracellular Matrix
  • Extracellular Matrix Proteins
  • Female
  • Humans
  • Mice
  • Picornaviridae Infections
  • Poly I-C
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8

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