Respiratory syncytial virus infection reduces lung inflammation and fibrosis in mice exposed to vanadium pentoxide.
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.
Turpin
Elizabeth A
EA
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Antao-Menezes
Aurita
A
Cesta
Mark F
MF
Mangum
James B
JB
Wallace
Duncan G
DG
Bermudez
Edilberto
E
Bonner
James C
JC
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D011014:Pneumonia / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications* / Q000378:metabolism*; D017968:Vanadium Compounds
D016207:Cytokines; D017968:Vanadium Compounds; C066075:vanadium pentoxide