Mutated glutathione-S-transferase reduced airway inflammation by limiting oxidative stress and Th2 response.
Oxidative stress is an important factor in the pathogenesis of asthma. Furthermore, antioxidants like GST are reduced in asthma patients. In the present study, the therapeutic effects of exogenous GST and mGST were evaluated in a mice model. GST mutated at residues 21/27 has reduced IgE binding with similar enzyme activity as that of GST. To evaluate the therapeutic effects of GST, BALB/c mice were immunized and challenged with ovalbumin. Mice were given GST, mGST, and alpha-lipoic acid by inhalation and sacrificed on Day 31 to evaluate inflammation and oxidative stress. Mice treated with mGST showed significantly reduced total cell count (P<0.01) and eosinophils (P<0.01) in BALF compared to GST- or PBS-treated groups. The lung inflammation score was lowest for the mGST-treated group along with reduced IL-4 (P<0.01) and OVA-specific IgE than other groups. Oxidative stress as per the lipid peroxidation level in BALF of mGST-treated mice was reduced significantly in comparison to PBS- or GST-treated mice. In conclusion, inhalation of mGST reduced airway inflammation in mice. Mutated GST with reduced allergenicity has better therapeutic potential and can be explored as an adjunct therapy in asthma.
Tripathi
Prabhanshu
P
Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
Singh
B P
BP
Arora
Naveen
N
D000818:Animals; D001665:Binding Sites; D001992:Bronchoalveolar Lavage Fluid; D002942:Circular Dichroism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000276:immunology; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008171:Lung Diseases / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010047:Ovalbumin; D018384:Oxidative Stress; D018418:Th2 Cells / Q000276:immunology*; D008063:Thioctic Acid / Q000494:pharmacology
D007073:Immunoglobulin E; D008063:Thioctic Acid; D010047:Ovalbumin; D005982:Glutathione Transferase