Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice
Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice
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DOI：
10.1159/000110891
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发表时间：
2008-01-01
影响因子：
2.8
通讯作者：
Kanehiro, Arihiko
中科院分区：
文献类型：
--
作者：
Ito, Wataru;Tanimoto, Mitsune;Kanehiro, Arihiko
背景：为明确生长因子是否在哮喘早期气道高反应性（AHR）和气道炎症的发展中起关键作用，在哮喘小鼠模型中分析生长因子与气道高反应性（AHR）和气道炎症的关系。方法：观察卵清蛋白（OVA）致敏和激发后气道功能、炎症、细胞因子和生长因子水平。结果：吸入甲胆碱的AHR在6 h升高，48 h达到峰值，持续14 d。支气管肺泡灌洗液中IL-4和IL-5水平在6 h升高，24 h达到峰值，但很快恢复到基线水平。IL-13水平升高至14天，在48小时达到峰值。BAL液体转化生长因子- β(1)和血小板衍生生长因子在12小时升高，并在14天保持升高。24-28天神经生长因子水平升高。BAL液体肝细胞生长因子（HGF）在12 h检测，24 h达到峰值，72 h恢复到基线水平。c-Met/HGF受体在BAL中HGF出现之前的6 h检测到，并在最后一次OVA攻毒后96 h继续观察。结论：这些数据确定了生长因子产生和Th2细胞因子产生与AHR动力学之间的时间关联。生长因子可能在过敏性气道炎症和AHR的发展中发挥重要作用，甚至在哮喘的早期阶段，在重塑开始之前。版权所有(c) 2007 S. Karger AG，巴塞尔。
Background: To clarify whether growth factors play critical roles in the development of airway hyperresponsiveness (AHR) and airway inflammation in the early stages of asthma, the relationship between growth factors and AHR and airway inflammation were analyzed in a mouse model of asthma. Methods: Following ovalbumin ( OVA) sensitization and challenge, airway function, inflammation, cytokine and growth factor levels were monitored. Results: AHR to inhaled methacholine increased at 6 h, peaked at 48 h, and remained elevated for 14 days. IL-4 and IL-5 levels in bronchoalveolar lavage (BAL) fluid were increased at 6 h, peaked at 24 h, but returned to baseline quickly. IL-13 levels increased up to 14 days, peaking at 48 h. Increases in BAL fluid transforming growth factor-beta(1) and platelet-derived growth factor were observed at 12 h, and remained elevated at 14 days. Nerve growth factor levels were increased at 24-28 days. BAL fluid hepatocyte growth factor (HGF) was detected at 12 h, peaked at 24 h, and returned to baseline by 72 h. c-Met/HGF receptor was detected in the airways at 6 h, before HGF in the BAL, and continued to be observed 96 h after the last OVA challenge. Conclusions: These data identify a temporal association between growth factor production and Th2 cytokine production and the kinetics of AHR. Growth factors may play important roles in the development of allergic airway inflammation and AHR even in the early stages of asthma, before remodeling is initiated. Copyright (c) 2007 S. Karger AG, Basel.