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Title: Chronic arsenic exposure in nanomolar concentrations compromises wound response and intercellular signaling in airway epithelial cells.

Authors: Sherwood, Cara L; Lantz, R Clark; Boitano, Scott

Published In Toxicol Sci, (2013 Mar)

Abstract: Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4-5 weeks and examined for wound repair efficiency and ATP-mediated Ca(2+) signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca(2+) signaling. We further show that arsenic compromises ATP-mediated Ca(2+) signaling by altering both Ca(2+) release from intracellular stores (via metabotropic P2Y receptors) and Ca(2+) influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca(2+) signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca(2+) signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10-50 ppb) alters cellular mechanisms critical to airway innate immunity.

PubMed ID: 23204110 Exiting the NIEHS site

MeSH Terms: Animals; Arsenic/toxicity*; Bronchi/cytology; Bronchi/drug effects*; Bronchi/metabolism; Calcium Signaling/drug effects*; Cell Line, Transformed; Dose-Response Relationship, Drug; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Real-Time Polymerase Chain Reaction; Receptors, Purinergic P2X/metabolism; Receptors, Purinergic P2Y/metabolism; Wound Healing/drug effects*

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