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- Title
Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo.
- Authors
KUO, Curtis; LIM, Sam; KING, Nicholas J.C.; BARTLETT, Nathan W.; WALTON, Ross P.; ZHU, Jie; GLANVILLE, Nicholas; ANISCENKO, Julia; JOHNSTON, Sebastian L.; BURGESS, Janette K.; BLACK, Judith L.; OLIVER, Brian G.
- Abstract
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. 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. 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. 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. Airway remodelling, as indicated by increased extracellular matrix production, was induced by rhinovirus in both in vitro and in vivo models. This study provides important information on the aetiology of asthmatic airway remodelling, which is integral to the pathogenesis of asthma.
- Subjects
RHINOVIRUSES; AIRWAY (Anatomy); ASTHMA; VIRUS diseases; EXTRACELLULAR matrix proteins; FIBROBLASTS; DISEASE exacerbation; EPITHELIAL cells
- Publication
Respirology, 2011, Vol 16, Issue 2, p367
- ISSN
1323-7799
- Publication type
Article
- DOI
10.1111/j.1440-1843.2010.01918.x