The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects
The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects
复制标题
DOI：
10.1016/j.jaci.2009.07.036
复制
发表时间：
2009-12-01
影响因子：
14.2
通讯作者：
Peden, David B.
中科院分区：
文献类型：
--
作者：
Alexis, Neil E.;Zhou, Haibo;Peden, David B.
背景资料：据报道，谷胱甘肽-S-转移酶Mu 1（GSTM 1）缺失基因型是与环境空气臭氧水平增加相关的急性呼吸道疾病的危险因素。众所周知，臭氧会立即导致肺功能下降和气道炎症增加。然而，目前还不知道是否GSTM 1调节这些臭氧反应在体内人类subjects.Objective：本研究的目的是确定是否GSTM 1空基因型调节臭氧反应在人类subjects.Methods：三十-对5名健康志愿者进行了GSTM 1无效突变的基因分型，并进行了标准的臭氧暴露方案，以确定肺功能和对臭氧的炎症反应是否与对照组不同。结果：GSTM 1对急性臭氧损伤肺功能无明显影响。粒细胞内流4小时后的挑战是相似的GSTM 1正常和null志愿者。然而，GSTM 1空志愿者有显着增加气道中性粒细胞24小时后的挑战，以及增加的HLA-DR对气道巨噬细胞和树突状细胞的表达。结论：GSTM 1空基因型与增加气道炎症24小时后臭氧暴露，这是一致的滞后时间之间观察到的增加环境空气臭氧暴露和肺部疾病的恶化。（J Allergy Clin Immunol 2009;124：1222-8.）
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. (J Allergy Clin Immunol 2009;124:1222-8.)