Adenovirus IL-13-induced airway disease in mice: a corticosteroid-resistant model of severe asthma.

Authors: Therien, AG  Bernier, V  Weicker, S  Tawa, P  Falgueyret, JP  Mathieu, MC  Honsberger, J  Pomerleau, V  Robichaud, A  Stocco, R  Dufresne, L  Houshyar, H  Lafleur, J  Ramachandran, C  O'Neill, GP  Slipetz, D  Tan, CM 
Citation: Therien AG, etal., Am J Respir Cell Mol Biol. 2008 Jul;39(1):26-35. Epub 2008 Feb 7.
Pubmed: (View Article at PubMed) PMID:18258919
DOI: Full-text: DOI:10.1165/rcmb.2007-0240OC

Interleukin 13 (IL-13) is considered to be a key driver of the development of airway allergic inflammation and remodeling leading to airway hyperresponsiveness (AHR). How precisely IL-13 leads to the development of airway inflammation, AHR, and mucus production is not fully understood. In order to identify key mediators downstream of IL-13, we administered adenovirus IL-13 to specifically induce IL-13-dependent inflammation in the lungs of mice. This approach was shown to induce cardinal features of lung disease, specifically airway inflammation, elevated cytokines, AHR, and mucus secretion. Notably, the model is resistant to corticosteroid treatment and is characterized by marked neutrophilia, two hallmarks of more severe forms of asthma. To identify IL-13-dependent mediators, we performed a limited-scale two-dimensional SDS-PAGE proteomic analysis and identified proteins significantly modulated in this model. Intriguingly, several identified proteins were unique to this model, whereas others correlated with those modulated in a mouse ovalbumin-induced pulmonary inflammation model. We corroborated this approach by illustrating that proteomic analysis can identify known pathways/mediators downstream of IL-13. Thus, we have characterized a murine adenovirus IL-13 lung model that recapitulates specific disease traits observed in human asthma, and have exploited this model to identify effectors downstream of IL-13. Collectively, these findings will enable a broader appreciation of IL-13 and its impact on disease pathways in the lung.

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RGD ID: 4145639
Created: 2010-11-11
Species: All species
Last Modified: 2010-11-11
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.