OX40/OX40L及IL-4在哮喘动物模型气道壁的表达
2010/08/20
背景：哮喘动物模型显示，共刺激分子OX40及其配体OX40L介导过敏性气道炎症的关键环节，后者包括嗜酸粒细胞气道炎症，气道高反应性及Th2的极化。研究者检测不同病情程度哮喘的OX40/OX40L及IL-4表达情况。
方法：该研究获得了27例哮喘患者支气管活检标本，其中轻度（GINA分级为1级）10例，中度（GINA分级为2-3级）7例，重度（GINA分级为4-5级）10例，以及13例健康对照。对固有层和气道平滑肌（ASM）束中OX40+、OX40L+、IL-4+及IL-4Rα+细胞数目，平滑肌束IL-4Rα+表达密度进行了检测。
结果：与健康对照组比较，轻度哮喘而非中、重度哮喘的固有层OX40+、OX40L+、IL-4+细胞数目，ASM束中IL-4+细胞数目明显增加。哮喘患者中，OX40/OX40L表达与固有层嗜酸粒细胞和IL-4+细胞数目呈正相关。与对照组比较，中、重度而非轻度哮喘的固有层IL-4Rα+细胞数目明显增加。平滑肌束IL-4Rα表达，组间比较无明显差异。
结论：在轻度而非中、重度哮喘的支气管粘膜下层，OX40/OX40L表达明显增加，且与组织嗜酸粒细胞增多及IL-4表达程度相关。这些共刺激分子是否能作为哮喘治疗靶点需要进一步研究。
（王刚 四川大学华西医院中西医结合科呼吸组 610041 摘译）
(Chest; 2010; 137(4): 797-804)
(Chest; 2010; 137(4): 797-804)
Airway wall expression of OX40/OX40L and interleukin-4 in asthma.
Siddiqui S, Mistry V, Doe C, Stinson S, Foster M, Brightling C.
Chest; 2010; 137(4): 797-804
Background: The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2 polarization. We sought to examine OX40/OX40L and interleukin (IL)-4 expression in asthma across severities.
Methods: Bronchial biopsies were obtained from 27 subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n=10], moderate GINA 2-3 [n=7], and severe GINA 4-5 [n=10]) and 13 healthy controls. The number of OX40+, OX40L+, IL-4+, and IL-4 receptor α (IL-4Rα)+ cells in the lamina propria and airway smooth muscle (ASM) bundle and the intensity of IL-4Rα+ expression by the ASM were assessed.
Results: The number of OX40+, OX40L+, and IL-4+ cells in the lamina propria and OX40+ and IL-4+ cells in the ASM bundle was significantly increased in subjects with mild asthma, but not in those with moderate or severe asthma, compared with healthy controls. In the subjects with asthma, OX40/OX40L expression was positively correlated with the number of eosinophils and IL-4+ cells in the lamina propria. The number of IL-4Rα+ cells in the lamina propria was significantly increased in moderate-to-severe disease, but not in mild asthma, compared with controls. IL-4Rα expression by the ASM bundle was not different among groups.
Conclusions: OX40/OX40L expression is increased in the bronchial submucosa in mild asthma, but not in moderate-to-severe disease, and is related to the degree of tissue eosinophilia and IL-4 expression. Whether these costimulatory molecules have a role as targets for asthma requires further investigation.
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牛奶过敏是学龄期儿童支气管高反应性和气道炎症的预测因子
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有氧训练逆转哮喘模型小鼠的气道炎症和气道重构
