title: Vasoactive Intestinal Peptide Knockout (VIP KO) mouse model of sulfite-sensitive asthma: up-regulation of novel lung carbonyl reductase.
abstract: BACKGROUND
  We earlier reported spontaneous features of asthma in Vasoactive Intestinal Peptide knockout mice (VIP KO): 1) peribronchiolar airway inflammation, with accumulation of lymphocytes and eosinophils, 2) pro-inflammatory cytokine production of IL-5, IL-6, with IFN-γ, and 3) airway hyper-responsiveness to inhaled methacholine. In human asthma, a phenotype with sulfite sensitivity leads to airway inflammation and hyper-responsiveness to inhaled sulfites, and is associated with upregulation of anti-oxidant protein lung carbonyl reductase. For the present experiments, we examined the role of VIP in modulating anti-oxidant genes and their proteins, including lung carbonyl reductase.
  
  
  RESULTS
  Four male VIP KO mice and four wild-type age- and gender matched mice had lungs examined for whole genome microarray and a proteomics approach using mass spectrometry. The proteomics analysis revealed that a novel variant of anti-oxidant protein lung carbonyl reductase (car3) was uniquely and markedly elevated in the VIP KO mice. RT-PCR indicated that carbonic anhydrase 3, which is an anti-oxidant protein, was elevated in the VIP KO mice.
  
  
  CONCLUSIONS
  These data support the concept that VIP influences the endogenous oxidant/antioxidant balance. One potential implication is that VIP and its analogues may be used to treat inflammatory diseases, including asthma.
authors: Department of Medicine, SUNY Stony Brook School of Medicine, Stony Brook, NY, USA. anthony.szema@sbumed.org
authors: Anthony M
authors: AM
authors: Szema
authors: Sayyed A
authors: SA
authors: Hamidi
authors: Antonius
authors: A
authors: Koller
authors: Dwight W
authors: DW
authors: Martin
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008168:Lung / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020543:Proteome; D040901:Proteomics / Q000379:methods; D013447:Sulfites / Q000009:adverse effects*; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000235:genetics* / Q000378:metabolism
chemical_list: D020543:Proteome; D013447:Sulfites; D014660:Vasoactive Intestinal Peptide; D000429:Alcohol Oxidoreductases