期刊
ALLERGY
卷 70, 期 5, 页码 514-521出版社
WILEY-BLACKWELL
DOI: 10.1111/all.12590
关键词
asthma; early allergic reaction; exacerbations; interleukin-33; serotonin
资金
- Swedish Research Council Medicine and Health
- Swedish Heart and Lung Foundation
- Konsul Th C Berghs research foundation
- Ollie and Elof Ericssons foundation
- Hesselmans research foundation
- Centre for Allergy Research at Karolinska Institutet
- Karolinska Institutet Foundation
BackgroundInterleukin-33 (IL-33) is implicated as an epithelium-derived danger signal promoting Th2-dependent responses in asthma. We hypothesized that IL-33 might also have direct effects on mast cell-driven allergic airway obstruction. MethodsThe effects of IL-33 on allergic responses in the airways of sensiti-zed mice were assessed both invivo and exvivo, as well as on cultured mast cells invitro. ResultsIn vivo, the allergen-induced increase in resistance in the conducting airways was enhanced in mice pretreated with IL-33. Also, in the isolated airways, the allergen-induced contractions were increased in preparations from animals subjected to intranasal IL-33 pretreatment. These effects invivo and exvivo were blocked by the 5-HT2A receptor antagonist ketanserin and absent in mice without mast cells. Likewise, the IL-33-induced enhancement of the allergen response was absent in isolated airways from mice lacking the IL-33 receptor. Moreover, exposure to IL-33 increased secretion of serotonin from allergen-challenged isolated airways. In cultured mast cells, IL-33 enhanced the expression of tryptophan hydroxylase 1, serotonin synthesis, and storage, as well as the secretion of serotonin following IgE receptor cross-linking. ConclusionThese results demonstrate that IL-33 exacerbates allergic bronchoconstriction by increasing synthesis, storage, and secretion of serotonin from the mast cell. This mechanism has implications for the development of airway obstruction in asthma.
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