Influence of cigarette smoke on the arginine pathway in asthmatic airways: Increased expression of arginase I
Influence of cigarette smoke on the arginine pathway in asthmatic airways: Increased expression of arginase I
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DOI：
10.1016/j.jaci.2006.10.030
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发表时间：
2007-02-01
影响因子：
14.2
通讯作者：
Hamid, Qutayba
中科院分区：
文献类型：
--
作者：
Bergeron, Celine;Boulet, Louis-Philippe;Hamid, Qutayba
背景：多达30%的哮喘受试者是吸烟者，吸烟可能是哮喘病理的重要因素。诱导型一氧化氮合酶(INOS)、鸟氨酸脱羧酶(ODC)和精氨酸酶I参与了精氨酸途径。我们已经证明精氨酸酶I和诱导型一氧化氮合酶在哮喘中上调。据报道，吸烟的哮喘患者呼出的一氧化氮水平较低。吸烟对哮喘患者精氨酸酶I表达的影响尚不清楚。目的：研究吸烟者、非吸烟者及尼古丁刺激后哮喘患者呼吸道精氨酸酶1、ODC和诱导型一氧化氮合酶(INOS)的表达。方法：对24例激素未治疗的轻度哮喘患者(吸烟者和非吸烟者各12例)进行支气管内活检。用免疫组织化学和原位杂交法检测精氨酸酶I、ODC和iNOS水平。结果：精氨酸酶I、ODC和诱导型一氧化氮合酶在两组哮喘患者的上皮和平滑肌束中均有表达。吸烟组与非吸烟组比较，精氨酸酶I和ODC免疫反应增强。INOS免疫反应性组间差异无统计学意义。尼古丁诱导气道上皮细胞和成纤维细胞精氨酸酶I和ODC的表达增加2倍。结论：本研究证实吸烟哮喘患者气道精氨酸酶I和ODC的表达较非吸烟哮喘患者明显增加，且尼古丁在体外可使其表达增加。临床意义：精氨酸酶I表达增加可能导致吸烟哮喘患者呼出的一氧化氮减少和慢性阻塞性肺病样气道重塑。
Background: Up to 30% of asthmatic subjects are smokers, and smoking might be an important contributor to asthma pathology. Inducible nitric oxide synthase (iNOS), ornithine decarboxylase (ODC), and arginase I are involved in the arginine pathway. We have shown that arginase I and iNOS are upregulated in asthma. Smoking asthmatic subjects are reported to have low exhaled nitric oxide levels. The effect of cigarette smoking on the expression of arginase I in asthma is unknown.Objectives: The aims of this study were to investigate the expression of arginase 1, ODC, and iNOS in asthmatic airways of smokers and nonsmokers and in vitro after nicotine stimulation.Methods: Endobronchial biopsies were performed on 24 steroid-naive subjects with mild asthma: 12 smokers and 12 nonsmokers. Arginase I, ODC, and iNOS levels were assessed by means of immunohistochemistry and in situ hybridization (arginase I). In vitro stimulation of airway cells with nicotine was performed, followed by real-time PCR.Results: Arginase I, ODC, and iNOS were expressed in the epithelium and smooth muscle bundles of both subgroups of asthmatic subjects. There was an increase of arginase I and ODC immunoreactivities in smoking compared with nonsmoking asthmatic subjects. There was no significant difference in immunoreactivity for iNOS between groups. Nicotine induced a 2-fold increase in arginase I and ODC expression in airway epithelial cells and fibroblasts.Conclusion: This study demonstrates that the expression of arginase I and ODC is increased in airways of smoking compared with nonsmoking asthmatic subjects and in vitro by nicotine.Clinical implications: Increased expression of arginase I might lead to low exhaled nitric oxide and chronic obstructive pulmonary disease-like airway remodeling in smoking asthmatic subjects.