Asthma and lower airway diseaseDownregulation of glutathione S-transferase pi in asthma contributes to enhanced oxidative stress
Section snippets
Subjects
Recruitment, nasal mucosal sampling, and RNA isolation from children with and without asthma were previously described.22 Briefly, after institutional review board approval was obtained, healthy and asthmatic children (age 5-18 years old) presenting to Cincinnati Children’s Hospital Medical Center were invited to participate in the study. Asthma was diagnosed in accordance with American Thoracic Society criteria.7, 8 All the children had positive skin prick test responses to at least 1
GSTPi expression and total GST activity are decreased in allergen-challenged mice
We examined GSTPi expression and total GST activity in several different murine models of asthma. Challenge with HDM or A fumigatus induced a significant increase in AHR, as measured by means of APTI after allergen challenge, as previously expected (data not shown). Contrary to expectations, we observed a marked decrease in the level of GSTPi mRNA expression in the lungs of mice after HDM or A fumigatus challenge compared with that seen in control mice (Fig 1, A and C). We also observed a
Discussion
The contribution of GSTPi to asthma has been supported by epidemiologic, genetic, and animal studies by our group and others,14, 15, 16, 17, 21 although the mechanism for this has remained elusive. Our findings provide important novel insights into the contribution of GSTPi to asthma in human subjects and mice. Given that several environmental exposures associated with asthma result in enhanced oxidative stress, one might predict that GST enzymes would be induced to increase the capacity to
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Cited by (0)
Supported by National Institutes of Health grant U19A170235 (G.K.K.H.).
Disclosure of potential conflict of interest: T. LeCras receives research support from the National Institutes of Health (NIH) and the American Heart Association. A. M. Fitzpatrick receives research support from the NIH; the National Heart, Lung, and Blood Institute; and the National Institute of Nursing Research. G. K. K. Hershey receives research support from the NIH. The rest of the authors have declared that they have no conflict of interest.