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

• Main Authors: Mangum James B, Cesta Mark F, Antao-Menezes Aurita, Turpin Elizabeth A, Wallace Duncan G, Bermudez Edilberto, Bonner James C
• Format: Article
• Language: English
• Published: BMC 2010-02-01
• Series: Respiratory Research
• Online Access: http://respiratory-research.com/content/11/1/20

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>In this study we investigated the effect of RSV pre- or post-exposure to V₂O₅in male AKR mice. Mice were pre-exposed by intranasal aspiration to RSV or media vehicle prior to intranasal aspiration of V₂O₅or saline vehicle at day 1 or day 7. A parallel group of mice were treated first with V₂O₅or saline vehicle at day 1 and day 7 then post-exposed to RSV or media vehicle at day 8.</p> <p>Results</p> <p>V₂O₅-induced airway inflammation and fibrosis were decreased by RSV pre- or post-exposure. Real time quantitative RT-PCR showed that V₂O₅significantly 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.</p> <p>Conclusions</p> <p>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.</p>