Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice.
The aim of the present study was to identify and validate the biological significance of new genes/proteins involved in the development of allergic airway disease in a murine asthma model. Gene microarrays were used to identify genes with at least a two-fold increase in gene expression in lungs of two separate mouse strains with high and low allergic susceptibility. Validation of mRNA data was obtained by western blotting and immunohistochemistry, followed by functional analysis of one of the identified genes in mice with targeted disruption of specific gene expression. Expression of two antioxidant enzymes, glutathione peroxidase-2 (GPX2) and glutathione S-transferase omega (GSTO) 1-1 was increased in both mouse strains after induction of allergic airway disease and localised in lung epithelial cells. Mice with targeted disruption of the Gpx-2 gene showed significantly enhanced airway inflammation compared to sensitised and challenged wild-type mice. Our data indicate that genes encoding the antioxidants GPX2 and GSTO 1-1 are common inflammatory genes expressed upon induction of allergic airway inflammation, and independently of allergic susceptibility. Furthermore, we provide evidence to illustrate the importance of a single antioxidant enzyme, GPX2, in protection from allergen-induced disease.
Dittrich
A M
AM
Dept of Paediatric Pneumology and Immunology, Charité Humboldt University, Germany.
Meyer
H-A
HA
Krokowski
M
M
Quarcoo
D
D
Ahrens
B
B
Kube
S M
SM
Witzenrath
M
M
Esworthy
R S
RS
Chu
F-F
FF
Hamelmann
E
E
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D010991:Plethysmography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D000485:Allergens; D002352:Carrier Proteins; C117709:Gsto1 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin; C492172:Gpx2 protein, mouse; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase