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

Cara L. Sherwood, Andrew E. Liguori, Colin E. Olsen, Robert Clark Lantz, Jefferey L Burgess, Scott A Boitano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere82970
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 6 2013

Fingerprint

Arsenic
arsenic
Cell culture
cell culture
Cell Culture Techniques
mice
Claudin-4
Occludin
epithelial cells
Epithelial Cells
Tight Junction Proteins
tight junctions
toxic substances
Lung
Lung Neoplasms
lungs
Claudin-1
Obstructive Lung Diseases
Pulmonary diseases
Phosphorylation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures. / Sherwood, Cara L.; Liguori, Andrew E.; Olsen, Colin E.; Lantz, Robert Clark; Burgess, Jefferey L; Boitano, Scott A.

In: PLoS One, Vol. 8, No. 12, e82970, 06.12.2013.

Research output: Contribution to journalArticle

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