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Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin

Authors
  • Smyth, Timothy1
  • Veazey, Janelle1
  • Eliseeva, Sophia2
  • Chalupa, David1
  • Elder, Alison1
  • Georas, Steve N.1, 1, 2
  • 1 University of Rochester, Rochester, NY, USA , Rochester (United States)
  • 2 University of Rochester, Box 692, 601 Elmwood Ave, University of Rochester, Rochester, NY, 14627, USA , Rochester (United States)
Type
Published Article
Journal
Particle and Fibre Toxicology
Publisher
BioMed Central
Publication Date
Oct 15, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12989-020-00383-x
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundWhile 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.Methods16HBE14o- 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.ResultsA six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentration-dependent 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.ConclusionShort 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.

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