Show simple item record Walker, JK Fong, AM Lawson, BL Savov, JD Patel, DD Schwartz, DA Lefkowitz, RJ
dc.coverage.spatial United States 2012-10-24T18:09:28Z 2003-08
dc.identifier 112/4/566
dc.identifier.citation J Clin Invest, 2003, 112 (4), pp. 566 - 574
dc.identifier.issn 0021-9738
dc.description.abstract Asthma is a chronic inflammatory disorder of the airways that is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. Migration of Th2 cells to the lung is key to their inflammatory function and is regulated in large part by chemokine receptors, members of the seven-membrane-spanning receptor family. It has been reported recently that T cells lacking beta-arrestin-2, a G protein-coupled receptor regulatory protein, demonstrate impaired migration in vitro. Here we show that allergen-sensitized mice having a targeted deletion of the beta-arrestin-2 gene do not accumulate T lymphocytes in their airways, nor do they demonstrate other physiological and inflammatory features characteristic of asthma. In contrast, the airway inflammatory response to LPS, an event not coordinated by Th2 cells, is fully functional in mice lacking beta-arrestin-2. beta-arrestin-2-deficient mice demonstrate OVA-specific IgE responses, but have defective macrophage-derived chemokine-mediated CD4+ T cell migration to the lung. This report provides the first evidence that beta-arrestin-2 is required for the manifestation of allergic asthma. Because beta-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, novel therapies focused on this protein may prove useful in the treatment of asthma.
dc.format.extent 566 - 574
dc.language eng
dc.relation.ispartof J Clin Invest
dc.relation.isversionof 10.1172/JCI17265
dc.subject Animals
dc.subject Antigens, CD3
dc.subject Antigens, CD4
dc.subject Arrestins
dc.subject Asthma
dc.subject Bronchoconstrictor Agents
dc.subject CD4-Positive T-Lymphocytes
dc.subject Cell Membrane
dc.subject Chemotaxis
dc.subject Cytokines
dc.subject Endotoxins
dc.subject Female
dc.subject Genotype
dc.subject Immunoglobulin E
dc.subject Immunoglobulin G
dc.subject Inflammation
dc.subject Lipopolysaccharides
dc.subject Lung
dc.subject Lymphocytes
dc.subject Macrophages
dc.subject Male
dc.subject Methacholine Chloride
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Transgenic
dc.subject Protein Structure, Tertiary
dc.subject T-Lymphocytes
dc.subject Th2 Cells
dc.subject Time Factors
dc.subject beta-Arrestin 2
dc.subject beta-Arrestins
dc.title Beta-arrestin-2 regulates the development of allergic asthma.
dc.type Journal Article
duke.description.endpage 574 en_US
duke.description.issue 4 en_US
duke.description.startpage 566 en_US
duke.description.volume 112 en_US
dc.relation.journal Journal of Clinical Investigation en_US
pubs.issue 4
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Biochemistry
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Cardiology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Nursing
pubs.organisational-group /Duke/Trinity College of Arts & Sciences
pubs.organisational-group /Duke/Trinity College of Arts & Sciences/Chemistry
pubs.publication-status Published
pubs.volume 112

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