Research

Respiratory syncytial virus infection reduces lung inflammation and fibrosis in mice exposed to vanadium pentoxide

Elizabeth A Turpin¹, Aurita Antao-Menezes¹, Mark F Cesta^1,2,3, James B Mangum¹, Duncan G Wallace¹, Edilberto Bermudez¹ and James C Bonner^1,3*

• * Corresponding author: James C Bonner james_bonner@ncsu.edu

Author Affiliations

¹ The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA

² Laboratory of Cellular and Molecular Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA

³ Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695, USA

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Respiratory Research 2010, 11:20 doi:10.1186/1465-9921-11-20

Published: 22 February 2010

Abstract

Background

Vanadium pentoxide (V₂O₅) exposure is a cause of occupational bronchitis and airway fibrosis. Respiratory syncytial virus (RSV) is a ubiquitous pathogen that causes airway inflammation. It is unknown whether individuals with pre-existing respiratory viral infection are susceptible to V₂O₅-induced bronchitis. We hypothesized that respiratory viral infection will exacerbate vanadium-induced lung fibrosis.

Methods

In this study we investigated the effect of RSV pre- or post-exposure to V₂O₅ in male AKR mice. Mice were pre-exposed by intranasal aspiration to RSV or media vehicle prior to intranasal aspiration of V₂O₅ or saline vehicle at day 1 or day 7. A parallel group of mice were treated first with V₂O₅ or saline vehicle at day 1 and day 7 then post-exposed to RSV or media vehicle at day 8.

Results

V₂O₅-induced airway inflammation and fibrosis were decreased by RSV pre- or post-exposure. Real time quantitative RT-PCR showed that V₂O₅ significantly increased lung mRNAs encoding pro-fibrogenic growth factors (TGF-β1, CTGF, PDGF-C) and collagen (Col1A2), but also increased mRNAs encoding anti-fibrogenic type I interferons (IFN-α, -β) and IFN-inducible chemokines (CXCL9 and CXCL10). RSV pre- or post-exposure caused a significantly reduced mRNAs of pro-fibrogenic growth factors and collagen, yet reduced RNA levels of anti-fibrogenic interferons and CXC chemokines.

Conclusions

Collectively these data suggest that RSV infection reduces the severity of V₂O₅-induced fibrosis by suppressing growth factors and collagen genes. However, RSV suppression of V₂O₅-induced IFNs and IFN-inducible chemokines suggests that viral infection also suppresses the innate immune response that normally serves to resolve V₂O₅-induced fibrosis.