@article{84fa9f41d375467e931ad3c3494949a0,
title = "The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects",
abstract = "Background: The glutathione-S-transferase Mu 1 (GSTM1) null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone levels. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. However, it is not known whether GSTM1 modulates these ozone responses in vivo in human subjects. Objective: The purpose of this study was to determine whether the GSTM1 null genotype modulates ozone responses in human subjects. Methods: Thirty-five healthy volunteers were genotyped for the GSTM1 null mutation and underwent a standard ozone exposure protocol to determine whether lung function and inflammatory responses to ozone were different between the 19 GSTM1 wild type and 16 GSTM1 null volunteers. Results: GSTM1 did not modulate lung function responses to acute ozone. Granulocyte influx 4 hours after challenge was similar between GSTM1 normal and null volunteers. However, GSTM1 null volunteers had significantly increased airway neutrophils 24 hours after challenge, as well as increased expression of HLA-DR on airway macrophages and dendritic cells. Conclusion: The GSTM1 null genotype is associated with increased airways inflammation 24 hours after ozone exposure, which is consistent with the lag time observed between increased ambient air ozone exposure and exacerbations of lung disease.",
keywords = "Glutathione-S-transferase Mu 1, dendritic cell, inflammation, macrophage, ozone, pollution, polymorphonuclear neutrophil",
author = "Alexis, {Neil E.} and Haibo Zhou and Lay, {John C.} and Bradford Harris and Hernandez, {Michelle L.} and Lu, {Tsui Shan} and Bromberg, {Philip A.} and David Diaz-Sanchez and Devlin, {Robert B.} and Kleeberger, {Steven R.} and Peden, {David B.}",
note = "Funding Information: Disclosure of potential conflict of interest: B. Harris has received research report from the National Institute of Environmental Health Sciences, the US Environmental Protection Agency, and Purdue Pharmaceuticals–Quintiles. P. A. Bromberg has received research support from the US Environmental Protection Agency and the National Institutes of Health. D. B. Peden has consulted for GlaxoSmithKline and Funxional Therapeutics and has received research support from the National Institute of Environmental Health Sciences; the National Center for Complementary and Alternative Medicine; the National Heart, Lung, and Blood Institute; the US Environmental Protection Agency; the National Center for Research Resources. The rest of the authors have declared that they have no conflict of interest. Funding Information: Supported by National Institutes of Health grants R01ES012706 , P30ES010126 , and P01AT002620 , US Environmental Protection Agency Cooperative Agreement CR 83346301, and the National Institute of Environmental Health Sciences Division of Intramural Research. Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through cooperative agreement CR-83346301 with the Center for Environmental Medicine and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency, and no official endorsement should be inferred. ",
year = "2009",
month = dec,
doi = "10.1016/j.jaci.2009.07.036",
language = "English",
volume = "124",
pages = "1222--1228.e5",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",
}
