ORCID Profile
0000-0003-0946-5050
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Publisher: Wiley
Date: 27-01-2011
DOI: 10.1111/J.1440-1843.2010.01918.X
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.
Publisher: Springer Science and Business Media LLC
Date: 02-2008
DOI: 10.1038/NM1713
Publisher: Springer Science and Business Media LLC
Date: 08-06-2018
DOI: 10.1038/S41467-018-04574-1
Abstract: Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor ( IFNAR1 −/− ) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1038/MI.2013.3
Publisher: EMBO
Date: 14-11-2012
Publisher: Public Library of Science (PLoS)
Date: 08-2013
Publisher: Wiley
Date: 28-11-2013
DOI: 10.1111/ALL.12329
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-08-2019
DOI: 10.1126/SCITRANSLMED.AAV3879
Abstract: Inhaled corticosteroids promote bacterial infection in chronic obstructive pulmonary disease by suppressing the antimicrobial peptide cathelicidin.
Publisher: Public Library of Science (PLoS)
Date: 26-09-2013
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nicholas Glanville.