title: Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo.
abstract: 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.
authors.affiliation: Discipline of Pharmacology, The University of Sydney, Camperdown, UK.
authors.forename: Curtis
authors.initials: C
authors.lastname: Kuo
authors.forename: Sam
authors.initials: S
authors.lastname: Lim
authors.forename: Nicholas J C
authors.initials: NJ
authors.lastname: King
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Bartlett
authors.forename: Ross P
authors.initials: RP
authors.lastname: Walton
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Nicholas
authors.initials: N
authors.lastname: Glanville
authors.forename: Julia
authors.initials: J
authors.lastname: Aniscenko
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
mesh_terms: D056151:Airway Remodeling; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000821:virology*; D001980:Bronchi / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D024062:Collagen Type V / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000821:virology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D051379:Mice; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists
chemical_list: D000634:Aminoquinolines; D024062:Collagen Type V; D016326:Extracellular Matrix Proteins; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D011070:Poly I-C; D000077271:Imiquimod