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    Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung

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    Article (1.154Mb)
    Supplemental material (115.4Kb)
    Date
    2009-03-04
    Author
    Kozul, Courtney D.  Concept link
    Hampton, Thomas H.  Concept link
    Davey, Jennifer C.  Concept link
    Gosse, Julie A.  Concept link
    Nomikos, Athena P.  Concept link
    Eisenhauer, Phillip L.  Concept link
    Weiss, Daniel J.  Concept link
    Thorpe, Jessica E.  Concept link
    Ihnat, Michael A.  Concept link
    Hamilton, Joshua W.  Concept link
    Metadata
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    Citable URI
    https://hdl.handle.net/1912/2871
    As published
    https://doi.org/10.1289/ehp.0800199
    DOI
    10.1289/ehp.0800199
    Keyword
     Arsenic; Inflammation; Innate immune system; Lung; Migration 
    Abstract
    Chronic exposure to drinking water arsenic is a significant worldwide environmental health concern. Exposure to As is associated with an increased risk of lung disease, which may make it a unique toxicant, because lung toxicity is usually associated with inhalation rather than ingestion. The goal of this study was to examine mRNA and protein expression changes in the lungs of mice exposed chronically to environmentally relevant concentrations of As in the food or drinking water, specifically examining the hypothesis that As may preferentially affect gene and protein expression related to immune function as part of its mechanism of toxicant action. C57BL/6J mice fed a casein-based AIN-76A defined diet were exposed to 10 or 100 ppb As in drinking water or food for 5–6 weeks. Whole genome transcriptome profiling of animal lungs revealed significant alterations in the expression of many genes with functions in cell adhesion and migration, channels, receptors, differentiation and proliferation, and, most strikingly, aspects of the innate immune response. Confirmation of mRNA and protein expression changes in key genes of this response revealed that genes for interleukin 1β, interleukin 1 receptor, a number of toll-like receptors, and several cytokines and cytokine receptors were significantly altered in the lungs of As-exposed mice. These findings indicate that chronic low-dose As exposure at the current U.S. drinking-water standard can elicit effects on the regulation of innate immunity, which may contribute to altered disease risk, particularly in lung.
    Description
    This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 117 (2009): 1108-1115, doi:10.1289/ehp.0800199.
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    • Josephine Bay Paul Center in Comparative Molecular Biology and Evolution
    Suggested Citation
    Environmental Health Perspectives 117 (2009): 1108-1115
     

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