| Role of hyaluronan and hyaluronan-binding proteins in human asthma. | |
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MedLine Citation:
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PMID: 21570715 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The characteristics of human asthma are chronic inflammation and airway remodeling. Hyaluronan, a major extracellular matrix component, accumulates during inflammatory lung diseases, including asthma. Hyaluronan fragments stimulate macrophages to produce inflammatory cytokines. We hypothesized that hyaluronan and its receptors would play a role in human asthma. OBJECTIVE: To investigate the role of hyaluronan and hyaluronan-binding proteins in human asthma. METHODS: Twenty-one subjects with asthma and 25 healthy control subjects underwent bronchoscopy with endobronchial biopsy and bronchoalveolar lavage. Fibroblasts were cultured, and hyaluronan and hyaluronan synthase expression was determined at baseline and after exposure to several mediators relevant to asthma pathobiology. The expression of hyaluronan-binding proteins CD44, TLR (Toll-like receptor)-2, and TLR4 on bronchoalveolar lavage macrophages was determined by flow cytometry. IL-8 production by macrophages in response to hyaluronan fragment stimulation was compared. RESULTS: Airway fibroblasts from patients with asthma produced significantly increased concentrations of lower-molecular-weight hyaluronan compared with those of normal fibroblasts. Hyaluronan synthase 2 mRNA was markedly increased in asthmatic fibroblasts. Asthmatic macrophages showed a decrease in cell surface CD44 expression and an increase in TLR2 and TLR4 expression. Macrophages from subjects with asthma showed an increase in responsiveness to low-molecular-weight hyaluronan stimulation, as demonstrated by increased IL-8 production. CONCLUSION: Hyaluronan homeostasis is deranged in asthma, with increased production by fibroblasts and decreased CD44 expression on alveolar macrophages. Upregulation of TLR2 and TLR4 on macrophages with increased sensitivity to hyaluronan fragments suggests a novel proinflammatory mechanism by which persistence of hyaluronan fragments could contribute to chronic inflammation and airway remodeling in asthma. |
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Authors:
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Jiurong Liang; Dianhua Jiang; Yoosun Jung; Ting Xie; Jennifer Ingram; Tony Church; Simone Degan; Maura Leonard; Monica Kraft; Paul W Noble |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-05-13 |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 128 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-02 Completed Date: 2011-10-24 Revised Date: 2012-02-03 |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 403-411.e3 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Division of Pulmonary, Allergy and Critical Care Medicine, Duke University School of Medicine, Durham, NC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Airway Remodeling Antigens, CD44 / genetics, metabolism* Asthma / immunology*, metabolism, physiopathology* Cytokines / biosynthesis Down-Regulation Female Fibroblasts / metabolism Glucuronosyltransferase / genetics, metabolism Humans Hyaluronic Acid / immunology*, metabolism Inflammation / immunology, metabolism Macrophages, Alveolar / metabolism Male Toll-Like Receptor 2 / genetics, metabolism Toll-Like Receptor 4 / genetics, metabolism Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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AI052201/AI/NIAID NIH HHS; HL06539/HL/NHLBI NIH HHS; HL77291/HL/NHLBI NIH HHS; P50-HL084917/HL/NHLBI NIH HHS; R01 AI052201-10/AI/NIAID NIH HHS; R01 HL060539-13/HL/NHLBI NIH HHS; R01 HL077291-07/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD44; 0/CD44 protein, human; 0/Cytokines; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 9004-61-9/Hyaluronic Acid; EC 2.4.1.17/Glucuronosyltransferase; EC 2.4.1.212/hyaluronan synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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