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

Authors

  • Curtis KUO,

    1. Discipline of Pharmacology
    2. ANZAC Research Institute, Concord Repatriation General Hospital, Concord
    Search for more papers by this author
  • Sam LIM,

    1. ANZAC Research Institute, Concord Repatriation General Hospital, Concord
    Search for more papers by this author
  • Nicholas J.C. KING,

    1. Discipline of Pathology, The University of Sydney, Camperdown
    Search for more papers by this author
  • Nathan W. BARTLETT,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Ross P. WALTON,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Jie ZHU,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Nicholas GLANVILLE,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Julia ANISCENKO,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Sebastian L. JOHNSTON,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, UK
    Search for more papers by this author
  • Janette K. BURGESS,

    1. Discipline of Pharmacology
    2. Woolcock Institute of Medical Research, Glebe, New South Wales, Australia
    Search for more papers by this author
  • Judith L. BLACK,

    1. Discipline of Pharmacology
    2. Woolcock Institute of Medical Research, Glebe, New South Wales, Australia
    Search for more papers by this author
  • Brian G. OLIVER

    Corresponding author
    1. Discipline of Pharmacology
    2. ANZAC Research Institute, Concord Repatriation General Hospital, Concord
    3. Woolcock Institute of Medical Research, Glebe, New South Wales, Australia
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: CORRIGENDUM Volume 17, Issue 1, 192, Article first published online: 21 December 2011

Brian G. Oliver, Discipline of Pharmacology, The University of Sydney, Sydney, NSW 2006, Australia. Email: brian.oliver@sydney.edu.au

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.

Ancillary