Estrogen stimulates Th2 cytokine production and regulates the compartmentalisation of eosinophils during allergen challenge in a mouse model of asthma
Date
2012
Authors
Cai, Yeping
Zhou, Jiansheng
Webb, Dianne
Journal Title
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Volume Title
Publisher
S Karger AG
Abstract
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 α 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 aeroallergen 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.
Description
Keywords
Keywords: 12 hydroxyicosatetraenoic acid; allergen; estradiol; estrogen; estrogen receptor alpha; fulvestrant; interleukin 13; interleukin 5; methacholine; tamoxifen; animal cell; animal experiment; animal model; animal tissue; article; asthma; blood; bone marrow; Asthma; Eosinophils; Estrogen; IL-13; IL-5; Mucus
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Source
International Archives of Allergy and Immunology
Type
Journal article
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DOI
10.1159/000331437
Restricted until
2037-12-31