Estrogen Stimulates Th2 Cytokine Production and Regulates the Compartmentalisation of Eosinophils during Allergen Challenge in a Mouse Model of Asthma
Estrogen Stimulates Th2 Cytokine Production and Regulates the Compartmentalisation of Eosinophils during Allergen Challenge in a Mouse Model of Asthma
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DOI：
10.1159/000331437
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Webb, Dianne C.
中科院分区：
文献类型：
--
作者：
Cai, Yeping;Zhou, Jiansheng;Webb, Dianne C.
背景：女性在青春期后哮喘更为普遍这一现象表明雌激素会促进该疾病的发展。然而，大多数在哮喘啮齿动物模型中研究雌激素作用的实验都因依赖卵巢切除小鼠而变得复杂，在这些小鼠中，除雌激素外的其他激素也会减少。
方法：我们旨在通过在雌性小鼠中使用I型（他莫昔芬）或II型（ICI 182,780）拮抗剂，或在气传过敏原激发期间向雄性小鼠给予雌二醇，来了解雌激素对过敏性气道疾病的影响。
结果：拮抗剂表明雌激素促进了骨髓嗜酸性粒细胞的动员以及嗜酸性粒细胞向气道腔的迁移。这些发现在用雌二醇处理的雄性小鼠中得到了证实，其血液和气道中的嗜酸性粒细胞数量均增加。雌激素刺激杯状细胞增生和基础肺阻力，但对支气管黏膜下层嗜酸性粒细胞数量或乙酰甲胆碱诱导的气道高反应性影响较小。过敏性小鼠的CD4 + T细胞表达雌激素受体α，雌激素促进白细胞介素 - 5和白细胞介素 - 13的产生，并通过纵隔淋巴结细胞抑制类花生酸12 - HETE的产生。
结论：这些数据表明，在气传过敏原激发期间，雌激素刺激Th2细胞因子的产生，这可能与其抑制12 - HETE的能力有关。基础肺阻力、杯状细胞增生以及嗜酸性粒细胞的分布也受雌激素影响。然而，雌激素在刺激对乙酰甲胆碱诱导的肺阻力敏感性增强方面并不起主要作用。版权所有 (C) 2012 S. 卡尔格股份公司，巴塞尔
Background: The observation that asthma becomes more prevalent following puberty in females suggests estrogen potentiates the development of this disease. However, most studies examining the role of estrogen in rodent models of asthma are complicated by their reliance on ovariectomised mice in which hormones other than estrogen are also attenuated. Methods: We aimed to understand the influence of estrogen on allergic airway disease by using type I (tamoxifen) or type II (ICI 182,780) antagonists in female mice or delivering estradiol to male mice during aeroallergen challenge. Results: The antagonists showed that estrogen promoted both the mobilisation of bone marrow eosinophils and egression of eosinophils to the airway lumen. These findings were corroborated in male mice treated with estradiol, which increased eosinophil numbers in both blood and airways. Estrogen stimulated goblet cell hyperplasia and baseline lung resistance, but had little effect on the number of eosinophils in the bronchial submucosa or methacholine-induced airway hyperreactivity. Estrogen receptor alpha was expressed by CD4+ T cells from allergic mice, and estrogen promoted the production of IL-5 and IL-13, and suppressed the production of the eicosanoid 12-HETE by mediastinal lymph node cells. Conclusions: These data show that during aeroal-lergen challenge, estrogen stimulates Th2 cytokine production, which may be linked to its ability to suppress 12-HETE. Lung resistance at baseline, goblet cell hyperplasia and the compartmentalisation of eosinophils was also influenced by estrogen. However, estrogen does not play a major role in stimulating enhanced sensitivity to methacholine-induced lung resistance. Copyright (C) 2012 S. Karger AG, Basel