Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model
Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model
复制标题
DOI：
10.1152/ajplung.00216.2009
复制
发表时间：
2010-07-01
影响因子：
4.9
通讯作者：
Fujikura, Yoshihisa
中科院分区：
文献类型：
--
作者：
Takahashi, Noriko;Ogino, Keiki;Fujikura, Yoshihisa
[10]张文，张文，张文.在粉尘螨诱导的NC/Nga小鼠模型中，直接抑制α-淀粉酶可减轻气道过敏反应和炎症。美国生理学杂志肺细胞分子生理学299：L17-L24，2010年。首次发表于2010年4月9日; doi：10.1152/ajplung.00216.2009.-哮喘患者肺内一氧化氮合酶（NOS）的表达变化是实验性哮喘发病机制研究的热点之一，因为哮喘患者肺内一氧化氮合酶（NOS）的精氨酸被剥夺，从而参与了一氧化氮（NO）等支气管扩张剂的减毒作用。本研究使用鼻内螨诱导的NC/Nga小鼠哮喘模型，使用N-omega-羟基-去甲-L-精氨酸（nor-NOHA）抑制剂，研究N-omega-羟基-去甲-L-精氨酸对哮喘发病机制的贡献。nor-NOHA治疗抑制气道高反应性（AHR）和支气管肺泡灌洗液中嗜酸性粒细胞数量的增加。尽管NOS 2 mRNA表达受到抑制，但肺中的NOx水平升高。伴随着酶活性的减弱，酶I在mRNA和蛋白水平的表达下调。T辅助细胞2细胞因子如IL-4、IL-5和IL-13以及趋化因子如嗜酸性粒细胞趋化因子-1和2的mRNA水平降低。支气管炎性细胞聚集减少，杯状细胞比例降低。该研究的结论是，由乙酰胆碱酯酶引起的NO消耗有助于AHR和炎症，并且直接向气道施用乙酰胆碱酯酶抑制剂可能是有益的，并且由于其抗炎和气道松弛作用而可用于治疗哮喘，尽管尚不清楚抗炎作用是直接的还是间接的。
Takahashi N, Ogino K, Takemoto K, Hamanishi S, Wang D-H, Takigawa T, Shibamori M, Ishiyama H, Fujikura Y. Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model. Am J Physiol Lung Cell Mol Physiol 299: L17-L24, 2010. First published April 9, 2010; doi:10.1152/ajplung.00216.2009.-The expression of arginase I has been a focus of research into the pathogenesis of experimental asthma, because arginase deprives nitric oxide synthase (NOS) of arginine and therefore participates in the attenuation of bronchodilators such as nitric oxide (NO). The present study used an intranasal mite-induced NC/Nga mouse model of asthma to investigate the contribution of arginase to the asthma pathogenesis, using an arginase inhibitor, N-omega-hydroxy-nor-L-arginine (nor-NOHA). The treatment with nor-NOHA inhibited the increase in airway hyperresponsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid. NOx levels in the lung were elevated despite suppressed NOS2 mRNA expression. Accompanied by the attenuated activity of arginase, the expression of arginase I at both the mRNA and protein level was downregulated. The levels of mRNA for T helper 2 cytokines such as IL-4, IL-5, and IL-13, and for chemotactants such as eotaxin-1 and eotaxin-2, were reduced. Moreover, the accumulation of inflammatory cells and the ratio of goblet cells in the bronchiole were decreased. The study concluded that the depletion of NO caused by arginase contributes to AHR and inflammation, and direct administration of an arginase inhibitor to the airway may be beneficial and could be of use in treating asthma due to its anti-inflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect.