| Airway Fibroblasts in Asthma Manifest an Invasive Phenotype. | |
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MedLine Citation:
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PMID: 21471104 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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RATIONALE: Invasive cell phenotypes have been demonstrated in malignant transformation, but not in other diseases, such as asthma. Cellular invasiveness is thought to be mediated by transforming growth factor beta-1 (TGFβ1) and matrix metalloproteinases (MMPs). Interleukin-13 (IL-13) is a key TH2 cytokine that directs many features of airway remodeling through TGFβ1 and MMPs. OBJECTIVES: We hypothesized that, in human asthma, IL-13 stimulates increased airway fibroblast invasiveness via TGFβ1 and MMPs in asthma as compared to normal controls. METHODS: Fibroblasts were cultured from endobronchial biopsies in 20 subjects with mild asthma (FEV1: 90 ± 3.6% pred) and 17 normal controls (FEV1: 102 ± 2.9% pred) who underwent bronchoscopy. Airway fibroblast invasiveness was investigated using Matrigel chambers. IL-13 or IL-13 with TGF-β1 neutralizing antibody or pan-MMP inhibitor (GM6001) was added to the lower chamber as a chemoattractant. Flow cytometry and immunohistochemistry were performed in a subset of subjects to evaluate IL-13 receptor levels. MEASUREMENTS AND MAIN RESULTS: IL-13 significantly stimulated invasion in asthmatic airway fibroblasts, as compared to normal controls. Inhibitors of both TGFβ1 and MMPs blocked IL-13-induced invasion in asthma, but had no effect in normal controls. At baseline, in airway tissue, IL-13 receptors were expressed in significantly higher levels in asthma, as compared to normal controls. In airway fibroblasts, baseline IL-13Rα2 was reduced in asthma compared to normal controls. CONCLUSIONS: IL-13 potentiates airway fibroblast invasion through a mechanism involving TGF-β1 and MMPs. IL-13 receptor subunits are differentially expressed in asthma. These effects may result in IL-13-directed airway remodeling in asthma. |
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Authors:
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Jennifer L Ingram; Molly J Huggins; Tony D Church; Yuejuan Li; Dave C Francisco; Simone Degan; Rafael Firszt; Denise M Beaver; Njira L Lugogo; Ying Wang; Mary E Sunday; Paul W Noble; Monica Kraft |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-25 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: - ISSN: 1535-4970 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-4-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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