S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity.
S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity.
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DOI：
10.1371/journal.pone.0070351
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jaffar Z
中科院分区：
文献类型：
--
作者：
Ferrini ME;Simons BJ;Bassett DJ;Bradley MO;Roberts K;Jaffar Z
过敏性哮喘以Th 2型炎症为特征，导致气道高反应性、黏液高分泌和组织重塑。S-亚硝基谷胱甘肽还原酶（GSNOR）是一种参与调节细胞内S-亚硝基硫醇水平的醇脱氢酶。已显示GSNOR活性在人哮喘肺中升高，导致S-亚硝基硫醇减少，从而导致气道高反应性增加。使用过敏性气道炎症的小鼠模型，我们报告说，一种新的选择性抑制剂GSNOR，SPL-334，鼻内给药，引起气道高反应性，过敏原特异性T细胞和嗜酸性粒细胞的积累，并在肺中的粘液产生响应过敏原吸入显着减少。此外，SPL-334处理导致气道中Th 2细胞因子IL-5和IL-13的产生以及趋化因子CCL 11（嗜酸细胞活化趋化因子-1）的水平显著降低。总的来说，这些观察结果表明，GSNOR抑制剂不仅在降低气道高反应性方面有效，而且在限制由CD 4 + Th 2细胞介导的肺部炎症反应方面也有效。这些结果表明，抑制GSNOR可能为治疗过敏性气道炎症提供一种新的治疗方法。
Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1) in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation.
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DOI：
10.1164/rccm.200901-0158oc
发表时间：
2009-08-01
影响因子：
24.7
作者：
Que, Loretta G.;Yang, Zhonghui;Kraft, Monica
通讯作者：
Kraft, Monica
影响因子：
4.8
作者：
Sanghani, Paresh C.;Davis, Wilhelmina I.;Sanghani, Sonal P.
通讯作者：
Sanghani, Sonal P.
影响因子：
4.4
作者：
Jaffar, Z;Wan, KS;Roberts, K
通讯作者：
Roberts, K
DOI：
10.1084/jem.20020009
发表时间：
2002-06-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mattes J;Yang M;Mahalingam S;Kuehr J;Webb DC;Simson L;Hogan SP;Koskinen A;McKenzie AN;Dent LA;Rothenberg ME;Matthaei KI;Young IG;Foster PS
通讯作者：
Foster PS
DOI：
10.1152/ajplung.2000.279.4.l716
发表时间：
2000-10-01
影响因子：
4.9
作者：
Fang, KH;Johns, R;Gaston, B
通讯作者：
Gaston, B