Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin
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(2020) 17:52
RESEARCH
Open Access
Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin Timothy Smyth1, Janelle Veazey2, Sophia Eliseeva3, David Chalupa1, Alison Elder1 and Steve N. Georas1,2,3*
Abstract Background: While exposure to diesel exhaust particles has been linked to aberrant immune responses in allergic diseases such as asthma, little attention has been paid to their effects on the airway epithelial barrier. In this study, we sought to determine the effect of diesel exhaust exposure on airway epithelial barrier function and composition using in vitro and in vivo model systems. Methods: 16HBE14o- human bronchial epithelial cells were grown on collagen coated Transwell inserts and exposed to 5 to 50 μg/cm2 SRM 2975 diesel particulate matter (DEP) suspended in cell culture medium or vehicle controls. Changes in barrier function were assessed by measuring transepithelial electrical resistance (TEER) and permeability to 4 kDa FITC Dextran. Neonatal BALB/c mice were exposed to aerosolized DEP (255 ± 89 μg/m3; 2 h per day for 5 days) and changes in the tight junction protein Tricellulin were assessed 2 weeks post exposure. Results: A six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentrationdependent reduction in epithelial barrier integrity as measured by decreased TEER and increased permeability to 4 kDa FITC-Dextran. This reduction in epithelial barrier integrity corresponded to a significant reduction in expression of the tight junction protein Tricellulin. siRNA mediated knockdown of Tricellulin recapitulated changes in barrier function caused by DEP exposure. Neonatal exposure to aerosolized DEP caused a significant reduction in lung Tricellulin 2 weeks post exposure at both the protein and mRNA level. Conclusion: Short term exposure to DEP causes a significant reduction in epithelial barrier integrity through a reduction in the tight junction protein Tricellulin. Neonatal exposure to aerosolized DEP caused a significant and sustained reduction in Tricellulin protein and mRNA in the lung, suggesting that early life exposure to inhaled DEP may cause lasting changes in airway epithelial barrier function. Keywords: Diesel exhaust particles, Tricellulin, Tric, Airway epithelial barrier, Tight junction
Background Air pollution has long been linked to increased morbidity and mortality of pulmonary diseases such as COPD and asthma [1–4]. Increased exposure to airborne particulate * Correspondence: [email protected] 1 Department of Environmental Medicine, University of Rochester, Rochester, NY, USA 2 Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA Full list of author information is available at the end of the article
matter (PM) has been shown to strongly correlate with negative health outcomes, including reduced lung function [5], increased hospitalizations [6], and premature death [7]. Diesel exhaust particles (DEP), which result from the incomplete combusti
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