Lung lining fluid glutathione attenuates IL-13-induced asthma
Lung lining fluid glutathione attenuates IL-13-induced asthma
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DOI：
10.1165/rcmb.2007-0128oc
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发表时间：
2008-05-01
影响因子：
6.4
通讯作者：
Joyce-Brady, Martin
中科院分区：
文献类型：
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作者：
Lowry, Matthew H.;McAllister, Brian P.;Joyce-Brady, Martin
GGT（enu1）小鼠，缺乏γ -谷氨酰转移酶，不能代谢细胞外谷胱甘肽，发生细胞内谷胱甘肽缺乏和氧化应激。我们采用气管内IL-13诱导野生型（WT）和GGT（enu1）小鼠气道炎症和哮喘，以确定改变谷胱甘肽代谢对支气管哮喘的影响。WT和GGT小鼠出现相似程度的肺部炎症。相比之下，IL-13在WT小鼠中诱导气道上皮细胞黏液细胞增生、黏液蛋白和黏液蛋白相关基因表达、表皮生长因子受体mRNA和表皮生长因子受体激活，并伴有气道高反应性，而在GGT（enu1）小鼠中无此作用。肺衬里液（细胞外）谷胱甘肽在GGT（enu1）比WT肺高10倍，提供了增加的炎症相关活性氧的缓冲。在WT小鼠中对GGT的药理学抑制产生了类似的效果，表明肺衬里液谷胱甘肽可以防止上皮细胞诱导的哮喘。抑制肺内膜液GGT活性可能是预防和治疗哮喘的一种新的治疗方法。
GGT(enu1) mice, deficient in gamma-glutamyl transferase and unable to metabolize extracellular glutathione, develop intracellular glutathione deficiency and oxidant stress. We used intratracheal IL-13 to induce airway inflammation and asthma in wild-type (WT) and GGT(enu1) mice to determine the effect of altered glutathione metabolism on bronchial asthma. WT and GGT(enu1) mice developed similar degrees of lung inflammation. In contrast, IL-13 induced airway epithelial cell mucous cell hyperplasia, mucin and mucin-related gene expression, epidermal growth factor receptor mRNA, and epidermal growth factor receptor activation along with airway hyperreactivity in WT mice but not in GGT(enu1) mice. Lung lining fluid (extracellular) glutathione was 10-fold greater in GGT(enu1) than in WT lungs, providing increased buffering of inflammation-associated reactive oxygen species. Pharmacologic inhibition of GGT in WT mice produced similar effects, suggesting that the lung lining fluid glutathione protects against epithelial cell induction of asthma. Inhibiting GGT activity in lung lining fluid may represent a novel therapeutic approach for preventing and treating asthma.