title: Estrogen stimulates Th2 cytokine production and regulates the compartmentalisation of eosinophils during allergen challenge in a mouse model of asthma.
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.
authors.affiliation: Immunology Department, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Cai
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Zhou
authors.forename: Dianne C
authors.initials: DC
authors.lastname: Webb
mesh_terms: D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D004967:Estrogens / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D004967:Estrogens; D018793:Interleukin-13; D015848:Interleukin-5