Pro-fibrotic Effect of IL-9 Overexpression in a Model of Airway Remodeling

Unit of Industrial Toxicology and Occupational Medicine, Université catholique de Louvain, Avenue Mounier, 53.02, 1200 Brussels, Belgium.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 09/2007; 37(2):202-9. DOI: 10.1165/rcmb.2006-0397OC
Source: PubMed


IL-9 overexpression protects against alveolar fibrosis induced by crystalline silica particles. This cytokine is also involved in allergic asthma. In the present study, we examined the effect of IL-9 overexpression on the subepithelial fibrotic response, a feature of asthmatic remodeling, induced by chronic exposure to Alternaria alternata extract. IL-9-overexpressing mice (Tg5) and their wild-type counterparts (FVB) were intranasally exposed to A. alternata extract or PBS (controls) twice a week during 3 mo. At the end of the allergic challenge, enhanced pause (Penh) measured in response to methacholine and fibrotic parameters, such as collagen and fibronectin lung content, were significantly higher in Tg5 compared with FVB. Staining of lung sections with Masson's Trichrome also showed more collagen fibers in peribronchial areas of treated Tg5 mice. A similar recruitment of inflammatory cells was observed in challenged FVB and Tg5 mice, except for eosinophils, which were significantly more abundant in the lung of Tg5. High serum levels of IgE and IgG1 in both strains indicated that FVB and Tg5 developed a strong type 2 immune response. The concentration of the eosinophil chemoattractant RANTES and the profibrotic mediator connective tissue growth factor (CTGF) was higher in the BAL of challenged Tg5 than FVB. These results demonstrate a profibrotic role of IL-9 in an airway remodeling model, possibly involving eosinophils and CTGF. These data also highlight a dual role of IL-9 in lung fibrosis, being anti- or profibrotic depending on the alveolar or airway localization of the process, respectively.

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Available from: Jean-Christophe Renauld, Oct 16, 2015
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    • "Overexpression of IL-9 in murine models of asthma has been shown to cause airway inflammation with pulmonary infiltration of eosinophils and lymphocytes, airway obstruction, and mast cell hyperplasia [9,10,12]. In contrast, anti−IL-9 antibody therapy has led to reduced levels of AHR in murine models of allergen-induced asthma [13,14]. "
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