Arsenic alters tight junction expression, distribution and function in human airway epithelial cells

Abstract

The airway epithelium plays a role in the innate immune response, in part, due to a barrier that separates the air‐filled lumen from the underlying tissue. Three categories of membrane spanning tight junction proteins contribute to the establishment of this barrier, including, JAMs, Claudins, and Occludin. Arsenic is a natural metalloid toxicant that can accumulate in the lung via inhalation or ingestion. In animal and human studies, we and others have shown that arsenic ingestion can lead to altered lung function suggesting epithelial barrier dysfunction. In this report, we evaluated the effects of low‐level arsenic exposure on airway epithelial barrier function. We found that low levels of arsenic in growth medium delayed (30‐60 ppb) or prevented (290 ppb) the establishment of an airway epithelial monolayer in vitro. Addition of arsenic to pre‐formed in vitro monolayers reduced transepithelial resistance. Using immunocytochemistry, immunoblotting and quantitative real time RT‐PCR, we found that monolayers of airway epithelial cells exposed to 0, 60 or 290 ppb arsenic displayed altered and unique patterns of expression for JAM‐A, several Claudins (1, 2, 3, 4, 5, 7), and Occludin. In summary, exposure to environmentally significant doses of arsenic can induce functional and structural changes in the airway epithelial barrier. Grant Support: NIH P30‐ES006694, T32‐HL007249; EPA R832095.