Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

被引:23
作者
Bunting, Melissa M. [1 ]
Shadie, Alexander M. [1 ]
Flesher, Rylie P. [1 ]
Nikiforova, Valentina [1 ]
Garthwaite, Linda [1 ]
Tedla, Nicodemus [1 ]
Herbert, Cristan [1 ]
Kumar, Rakesh K. [1 ]
机构
[1] Univ New S Wales, Sch Med Sci, Inflammat & Infect Res Ctr, Dept Pathol, Sydney, NSW 2052, Australia
基金
英国医学研究理事会;
关键词
MURINE MODEL; ALLERGIC-ASTHMA; T-LYMPHOCYTES; INFECTION; LUNG; CYTOKINE; IL-33; HYPERREACTIVITY; EXPRESSION; EOSINOPHIL;
D O I
10.1155/2013/250938
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.
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页数:10
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