Adenovirus IL-13-induced airway disease in mice: a corticosteroid-resistant model of severe asthma.
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.
Therien
Alex G
AG
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada.
Bernier
Virginie
V
Weicker
Sean
S
Tawa
Paul
P
Falgueyret
Jean-Pierre
JP
Mathieu
Marie-Claude
MC
Honsberger
Jeanne
J
Pomerleau
Véronique
V
Robichaud
Annette
A
Stocco
Rino
R
Dufresne
Lynn
L
Houshyar
Hani
H
Lafleur
Josiane
J
Ramachandran
Chidambaram
C
O'Neill
Gary P
GP
Slipetz
Deborah
D
Tan
Christopher M
CM
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000503:physiopathology*; D000402:Airway Obstruction / Q000139:chemically induced*; D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D004195:Disease Models, Animal; D018793:Interleukin-13 / Q000009:adverse effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018793:Interleukin-13; D010047:Ovalbumin