| IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways. | |
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MedLine Citation:
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PMID: 20971830 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. Methods: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. Measurements and Main Results: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-β1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. Conclusions: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma. |
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Authors:
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Jennifer Kearley; Jonas S Erjefalt; Cecilia Andersson; Ebony Benjamin; Carla P Jones; Annette Robichaud; Sophie Pegorier; Yambasu Brewah; Timothy J Burwell; Leif Bjermer; Peter A Kiener; Roland Kolbeck; Clare M Lloyd; Anthony J Coyle; Alison A Humbles |
Publication Detail:
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Type: Journal Article Date: 2010-10-22 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 183 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-07 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 865-75 Citation Subset: AIM; IM |
Affiliation:
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Department of Respiratory, Inflammation, and Autoimmunity, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878. humblesa@medimmune.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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