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

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-beta1, CTGF, PDGF-C) and collagen (Col1A2), but also increased mRNAs encoding anti-fibrogenic type I interferons (IFN-alpha, -beta) 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.

• Authors: Elizabeth A Turpin, Aurita Antao-Menezes, Mark F Cesta, James B Mangum, Duncan G Wallace, Edilberto Bermudez, James C Bonner
• Journal: Respiratory research (Respir Res) Vol. 11 Pg. 20 (Feb 22 2010) ISSN: 1465-993X [Electronic] England
• PMID: 20175905 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Vanadium Compounds
• vanadium pentoxide

Topics

• Animals
• Cytokines (metabolism)
• Male
• Mice
• Mice, Inbred AKR
• Pneumonia (chemically induced, complications, metabolism)
• Pulmonary Fibrosis (chemically induced, complications, metabolism)
• Respiratory Syncytial Virus Infections (complications, metabolism)
• Vanadium Compounds