期刊
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
卷 158, 期 -, 页码 96-102出版社
KARGER
DOI: 10.1159/000337801
关键词
Severe asthma; Airway inflammation; Interleukin 8; interleukin 17; Neutrophils; Eosinophils
资金
- AstraZeneca
- Merck
- Glaxo-SmithKline
- Novartis
Neutrophils may play an important role in the pathogenesis of severe asthma. Their infiltration into the airway is increased. Interleukin (IL)-8 is involved in this process, and is actually upregulated in the airways of patients. We have observed that in the absence of eosinophil chemoattractants, neutrophils stimulated by IL-8 augment eosinophil trans-basement membrane migration by releasing superoxide anion, matrix metalloproteinase, leukotriene B-4 and platelet-activating factor. These findings suggest that IL-8-stimulated neutrophils could lead eosinophils to accumulate in the airways of asthmatic patients, which might be a mechanism for corticosteroid resistance in severe asthma. However, the mechanisms of IL-8 upregulation in the airway are not completely understood. Several studies suggest that IL-17 (or T helper 17 cells; Th17) is involved in the IL-8 upregulation observed in severe asthma. We clarified that dopamine induces Th17 differentiation through dopamine D1-like receptor (D1-like-R), and that the D1-like-R antagonist attenuates Th17-mediated diseases like experimental autoimmune encephalomyelitis. Furthermore, we demonstrated that a D1-like-R antagonist significantly suppressed ovalbumin (OVA)-induced neutrophilic airway inflammation in OVA T cell receptor-transgenic DO11.10 mice through inhibiting Th17-mediated immune responses. Therefore, dopamine D1-like-R antagonists could become useful for treating Th17-mediated neutrophil-dominant severe asthma. As inhaled corticosteroids are known to be less effective for controlling neutrophilic inflammation, a more effective therapeutic strategy for neutrophil-dominant asthma should still be elucidated. Copyright (C) 2012 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据