Anti-inflammatory Effect of Arginase Inhibitor and Corticosteroid on Airway Allergic Reactions in a Dermatophogoides farinae-induced NC/Nga Mouse Model
Anti-inflammatory Effect of Arginase Inhibitor and Corticosteroid on Airway Allergic Reactions in a Dermatophogoides farinae-induced NC/Nga Mouse Model
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DOI：
10.1007/s10753-012-9529-3
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发表时间：
2013-02-01
期刊：
影响因子：
5.1
通讯作者：
Fujikura, Yoshihisa
中科院分区：
文献类型：
--
作者：
Ogino, Keiki;Kubo, Masayuki;Fujikura, Yoshihisa
本研究的目的是探讨在鼻内螨诱导的NC/Nga小鼠哮喘模型中，一种抗哮喘酶抑制剂N-羟基-去甲-L-精氨酸（nor-NOHA）和一种皮质类固醇激素泼尼松龙的作用。nor-NOHA和泼尼松龙治疗可抑制气道高反应性的增加、支气管肺泡灌洗液细胞数的增加、肺泡灌洗液中一氧化氮合酶I和二氧化氮合酶II的蛋白表达、一氧化氮合酶（NOS）2和Th 2型细胞因子如白细胞介素（IL）-4、IL-5和IL-13的mRNA表达以及肺的病理性炎症改变。在用泼尼松龙处理的小鼠中，肺中的NOx水平没有改变，并且在用nor-NOHA或泼尼松龙加nor-NOHA处理的小鼠中升高，尽管抑制了NOS 2 mRNA表达。该研究得出的结论是，nor-NOHA的抗炎作用可能依赖于通过下调精氨酸酶的精氨酸利用率而从耗尽的NO中供应NO，而与泼尼松龙的抗炎机制无关。
The present study was aimed to investigate the effect of an arginase inhibitor, N-hydroxy-nor-l-arginine (nor-NOHA) and a corticosteroid, prednisolone, in an intranasal mite-induced NC/Nga mouse model of asthma. The treatment with nor-NOHA and prednisolone inhibited the increase in airway hyperresponsiveness, the number of bronchoalveolar lavage fluid cells, protein expression of arginase I and arginase II, messenger RNA (mRNA) expression of nitric oxide synthase (NOS)2 and Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13, and the pathological inflammatory changes of the lung. NOx levels in the lung were not changed in mice treated with prednisolone and elevated in mice treated with nor-NOHA or prednisolone plus nor-NOHA despite suppressed NOS2 mRNA expression. The study concluded that anti-inflammatory effect by nor-NOHA might be dependent on NO supply from depleted NO by downregulated arginine availability of arginase and was not related with the anti-inflammatory mechanisms by prednisolone.