Mutated Glutathione-S-Transferase Reduced Airway Inflammation In Murine Model

Article Outline

• Rationale
• Methods
• Results
• Conclusion
• Copyright

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Rationale 

Oxidative stress contributes in the pathogenesis of asthma. Glutathione-s-transferase (GST) is an antioxidant and its deficiency increases the risk of developing asthma. The present study investigates the effect of GST and mutated GST (mGST) with reduced IgE binding in murine model of airway inflammation.

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Methods 

BALB/c mice were immunized i.p. with ovalbumin (10μg/100μl PBS) on days 1 and 14 and challenged on days 28, 29, and 30. Mice were administered intranasally with GST, mGST, lipoic acid (LA) and PBS after 1 h of each OVA challenge. Mice were sacrificed on day 31 and lungs were used for histology. Total and differential cell count, IL-4, IFN-γ and oxidative stress were measured in BALF. Immunoglobulins were determined in sera.

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Results 

GST and mGST have similar enzymatic activity but mGST has reduced IgE binding (44% reduction). mGST mice showed significantly reduced total cell count and eosinophils in BALF as compared to PBS or GST administered groups (p < 0.01). Lung inflammation score in terms of eosinophilic infiltration and mucous secretion was lowest for LA group mice followed by mGST and GST administered groups. IL-4 was significantly reduced for mGST group compared to PBS administered or GST group mice (p < 0.01). However no change was observed in IgG subtypes. Oxidative stress in BALF of both mGST as well as GST administered mice were reduced significantly in comparision to PBS instilled group (p < 0.01).

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Conclusion 

These data suggests that mGST with reduced IgE binding has potential to limit airway inflammation in bronchial asthma.