Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures

• Published in: PloS one Vol. 8; no. 12; p. e82970
• Main Authors: Sherwood, Cara L, Liguori, Andrew E, Olsen, Colin E, Lantz, R Clark, Burgess, Jefferey L, Boitano, Scott
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.12.2013; Public Library of Science (PLoS)
• Subjects: Air Pollutants - toxicity; Animals; Arsenic; Arsenic - toxicity; Arsenites - adverse effects; Arsenites - pharmacology; Blood-Air Barrier - metabolism; Blood-Air Barrier - pathology; Cell Line, Transformed; Cells (Biology); Chronic obstructive pulmonary disease; Collaboration; Disease; Drinking water; Environmental Exposure - adverse effects; Environmental health; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacology; Epithelial cells; Exposure; Gene expression; Health sciences; Humans; Immune response; Immune system; Infections; Ingestion; Inhalation; Laboratories; Localization; Lung cancer; Lung diseases; Membrane proteins; Mice; mRNA; Obstructive lung disease; Occludin - metabolism; Particulates; Penicillin; Phosphatase; Phosphorylation; Phosphorylation - drug effects; Physiology; Proteins; Respiration; Respiratory function; Respiratory Mucosa - metabolism; Respiratory tract; RNA; Rodents; Sodium arsenite; Sodium Compounds - adverse effects; Sodium Compounds - pharmacology; Structure-function relationships; Tight Junctions - metabolism; Tight Junctions - pathology; Toxicants; Water pollution; United States > US; Arizona
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082970

Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.