The Antioxidants, Glutathione-S-Transferase-Omega1-1 (GST1-1) and Glutathione Peroxidase2 (GPX2), Are Increased in Allergic Airway Inflammation

Abstract

RATIONALE: Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering a multitude of inflammatory pathways. We attempted to delineate novel molecules that are yet not recognized as mediators and who operate independently of atopic susceptibility as common mediators of allergic pulmonary inflammation. METHODS: In a mouse model of allergen-induced sensitization and airway inflammation, RNA expression in whole lung tissues was compared between a high-IgE responder mouse strain (BALB/c) and mice with lower allergic susceptibility (C57/Bl6) by using microarray based RNA expression analysis. Results were confirmed by using western blot analysis of protein expression in murine lung tissues. Additionally, the location of target proteins was determined by immune histochemistry of murine and human airways. Finally, the functional relevance of the targets was assessed by using genetically deficient knock-out mice. RESULTS: The expression of two antioxidant enzymes involved in the glutathione pathway, GPX2 and GST1-1, was increased in both strains after induction of airway inflammation on the RNA level. Using western blot analysis a significant increase in protein expression was also found. GPX2 and GST1-1 were both located in the airway epithelium of murine and human lung tissues. Allergen sensitization and airway challenges of GPX2 knock-out mice resulted in hightened inflammatory airway responses, suggesting a protective role for this molecule. CONCLUSIONS: These data indicate that the antioxidants GPX2 and GST1-1 constitute common inflammatory genes, possibly serving as negative regulators inhibiting or counterbalancing the development of allergic airway inflammation.