Glutathione S-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke
Glutathione S-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke
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DOI：
10.1164/rccm.200509-1424oc
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发表时间：
2006-12-15
影响因子：
24.7
通讯作者：
Diaz-Sanchez, David
中科院分区：
文献类型：
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作者：
Gilliland, Frank D.;Li, Yu-Fen;Diaz-Sanchez, David
基本原理：二手烟草烟雾（SHS）和交通相关的空气污染物与哮喘和过敏有关。柴油机排气颗粒物（DEPs）和SHS可与过敏原相互作用，通过产生活性氧而加重过敏性气道疾病。目的：本研究旨在验证功能性GSTM 1缺失基因型和GSTP 1密码子105变异体在SHS和DEP中表达的假说，（11005和Val 105）是对SHS的过敏反应的决定因素，并且对SHS和DEP的反应是相关的。在一项随机、安慰剂对照的交叉试验中，19名先前参加过DEP试验的豚草过敏原敏感受试者在单独访问时暴露于清洁空气或SHS后鼻内接受过敏原挑战。鼻过敏原特异性IgE，组胺，IL-4和IFN-γ水平测定之前和之后过敏原challenge.Main结果：个人与GSTM 1-null或GSTP 1 Ile 105基因型表现出较大的鼻过敏原与SHS相比，干净的空气。在SHS加过敏原激发后，GSTM 1缺失受试者的IgE增加幅度大于GSTM 1存在受试者（中位数，173.3 vs. 46.7 U/ml; p = 0.03），Ile 105 GSTP 1基因型受试者的组胺增加（中位数，10.2 vs. 4.6 nM; p = 0.01）。对SHS和DEP的反应是相关的。结论：GSTM 1和GSTP 1是重要的细胞保护因子，可减轻SHS和DEP引起的过敏反应。
Rationale: Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEPs.Objectives: We tested the hypotheses that functional GSTM1-null genotype and GSTP1 codon 105 variants (11005 and Val105) are determinants of allergic responses to SHS, and that responses to SHS and DEPs are correlated.Methods and Measurements: In a randomized, placebo-controlled crossover trial, 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits. Nasal allergen-specific IgE, histamine, IL-4, and IFN-gamma levels were measured before and after allergen challenge.Main Results: Individuals with GSTM1-null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air. GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects (median, 173.3 vs. 46.7 U/ml; p = 0.03), and the Ile105 GSTP1 genotype subjects had increased histamine (median, 10.2 vs. 4.6 nM; p = 0.01) after SHS plus allergen challenge. Responses to SHS and DEPs were correlated. Enhancement of IgE and histamine was greatest in the subjects with both the GSTM1-null and GSTP1 Ile/Ile genotypes.Conclusions: GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses.