This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0397OCv1 37/2/202    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van den Brûle, S. Articles by Denis, O. Search for Related Content PubMed PubMed Citation Articles by van den Brûle, S. Articles by Denis, O.

Profibrotic Effect of IL-9 Overexpression in a Model of Airway Remodeling

Unit of Industrial Toxicology and Occupational Medicine, Cardiology Unit, and Unit of Experimental Medicine and Ludwig Institute for Cancer Research, Université catholique de Louvain; and Allergology Unit, WIV-Pasteur Institute of Brussels, Brussels, Belgium

Correspondence and requests for reprints should be addressed to Sybille van den Brûle, Unit of Industrial Toxicology and Occupational Medicine, Université catholique de Louvain, Avenue Mounier, 53.02, 1200 Brussels, Belgium. E-mail: Sybille.vandenBrule{at}uclouvain.be

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.

Key Words: IL-9 • chronic asthma • remodeling • fibrosis • Alternaria alternata

CLINICAL RELEVANCE We show that IL-9 exacerbates the chronic allergic reaction to the airborne mold Alternaria alternata and, more particularly, the airway remodeling. The profibrotic effect of IL-9 in this model is in contrast with its antifibrotic effect in silicosis.

 

This article has been cited by other articles:

				D. Lison, J. Laloy, I. Corazzari, J. Muller, V. Rabolli, N. Panin, F. Huaux, I. Fenoglio, and B. Fubini Sintered Indium-Tin-Oxide (ITO) Particles: A New Pneumotoxic Entity Toxicol. Sci., April 1, 2009; 108(2): 472 - 481. [Abstract] [Full Text] [PDF]