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

Cara L. Sherwood, R. Clark Lantz, Scott Boitano

Research output: Contribution to journalArticle

15 Scopus citations

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 Ca2+ signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca2+ signaling. We further show that arsenic compromises ATP-mediated Ca2+ signaling by altering both Ca2+ release from intracellular stores (via metabotropic P2Y receptors) and Ca2+ influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca2+ 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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)222-234
Number of pages13
JournalToxicological Sciences
Volume132
Issue number1
DOIs
StatePublished - Mar 1 2013

Keywords

  • 16HBE14o-
  • ATP
  • Airway innate immunity
  • Arsenic
  • Calcium signaling

ASJC Scopus subject areas

  • Toxicology

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