title: Adenovirus IL-13-induced airway disease in mice: a corticosteroid-resistant model of severe asthma.
abstract: 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.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Therien
authors.forename: Virginie
authors.initials: V
authors.lastname: Bernier
authors.forename: Sean
authors.initials: S
authors.lastname: Weicker
authors.forename: Paul
authors.initials: P
authors.lastname: Tawa
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Jeanne
authors.initials: J
authors.lastname: Honsberger
authors.forename: Véronique
authors.initials: V
authors.lastname: Pomerleau
authors.forename: Annette
authors.initials: A
authors.lastname: Robichaud
authors.forename: Rino
authors.initials: R
authors.lastname: Stocco
authors.forename: Lynn
authors.initials: L
authors.lastname: Dufresne
authors.forename: Hani
authors.initials: H
authors.lastname: Houshyar
authors.forename: Josiane
authors.initials: J
authors.lastname: Lafleur
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Ramachandran
authors.forename: Gary P
authors.initials: GP
authors.lastname: O'Neill
authors.forename: Deborah
authors.initials: D
authors.lastname: Slipetz
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tan
mesh_terms: 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
chemical_list: D018793:Interleukin-13; D010047:Ovalbumin