首页    期刊浏览 2025年07月08日 星期二
登录注册

文章基本信息

  • 标题:β2-Adrenoceptor signaling in airway epithelial cells promotes eosinophilic inflammation, mucous metaplasia, and airway contractility
  • 本地全文:下载
  • 作者:Long P. Nguyen ; Nour A. Al-Sawalha ; Sergio Parra
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2017
  • 卷号:114
  • 期号:43
  • 页码:E9163-E9171
  • DOI:10.1073/pnas.1710196114
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The mostly widely used bronchodilators in asthma therapy are β2-adrenoreceptor (β2AR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that β2AR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that β2AR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of β2AR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that β2AR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent β2AR ligand shows the receptors are highly expressed in airway epithelium. In β2AR−/− mice, transgenic expression of β2ARs only in airway epithelium is sufficient to rescue IL-13–induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of β-arrestin-2 (βarr-2−/−) attenuates the asthma phenotype as in β2AR−/− mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by β2AR signaling. Together, these results suggest β2ARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the β2AR involves βarr-2. These results identify β2AR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.
  • 关键词:asthma ; β2-adrenoceptor ; airway epithelium ; mucous metaplasia ; airway hyperresponsiveness
国家哲学社会科学文献中心版权所有