Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice
Glutathione peroxidase-2 protects from allergen-induced airway inflammation in mice
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DOI：
10.1183/09031936.00026108
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发表时间：
2010-05-01
影响因子：
24.3
通讯作者：
Hamelmann, E.
中科院分区：
文献类型：
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作者：
Dittrich, A. M.;Meyer, H-A.;Hamelmann, E.
本研究的目的是确定和验证在小鼠哮喘模型中参与变应性气道疾病发展的新基因/蛋白的生物学意义。基因微阵列被用来鉴定两种不同的高、低过敏易感性小鼠菌株的肺中基因表达至少增加两倍的基因。通过western blotting和免疫组织化学获得mRNA数据的验证，然后对鉴定的基因之一进行功能分析，靶向破坏特定基因的表达。两种抗氧化酶，谷胱甘肽过氧化物酶-2 （GPX2）和谷胱甘肽s -转移酶-1 (GSTO) - 1-1在诱导变应性气道疾病后均表达升高，并在肺上皮细胞中定位。靶向破坏Gpx-2基因的小鼠与致敏型和攻毒型野生型小鼠相比，气道炎症明显增强。我们的数据表明，编码抗氧化剂GPX2和GSTO 1-1的基因是过敏性气道炎症诱导时常见的炎症基因，且与过敏易感性无关。此外，我们提供证据来说明单一抗氧化酶GPX2在保护免受过敏原诱导疾病中的重要性。
The aim of the present study was to identify and validate the biological significance of new genes/proteins involved in the development of allergic airway disease in a murine asthma model.Gene microarrays were used to identify genes with at least a two-fold increase in gene expression in lungs of two separate mouse strains with high and low allergic susceptibility. Validation of mRNA data was obtained by western blotting and immunohistochemistry, followed by functional analysis of one of the identified genes in mice with targeted disruption of specific gene expression.Expression of two antioxidant enzymes, glutathione peroxidase-2 (GPX2) and glutathione S-transferase omega (GSTO) 1-1 was increased in both mouse strains after induction of allergic airway disease and localised in lung epithelial cells. Mice with targeted disruption of the Gpx-2 gene showed significantly enhanced airway inflammation compared to sensitised and challenged wild-type mice.Our data indicate that genes encoding the antioxidants GPX2 and GSTO 1-1 are common inflammatory genes expressed upon induction of allergic airway inflammation, and independently of allergic susceptibility. Furthermore, we provide evidence to illustrate the importance of a single antioxidant enzyme, GPX2, in protection from allergen-induced disease.