Diesel Exhaust Particle Exposure Reduces Expression of the Epithelial Tight Junction Protein Tricellulin

Overview

Journal Part Fibre Toxicol

Publisher Biomed Central

Specialty Toxicology

Date 2020 Oct 16

PMID 33059747

Citations 16

Authors

Timothy Smyth

Janelle Veazey

Sophia Eliseeva

David Chalupa

Alison Elder

Steve N Georas

Affiliations

Soon will be listed here.

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/cm 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/m; 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 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.

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.

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References

Nemmar A, Hoylaerts M, Hoet P, Nemery B . Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects. Toxicol Lett. 2004; 149(1-3):243-53. DOI: 10.1016/j.toxlet.2003.12.061. View

Jew K, Herr D, Wong C, Kennell A, Morris-Schaffer K, Oberdorster G . Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer's disease mice. Part Fibre Toxicol. 2019; 16(1):45. PMC: 6878709. DOI: 10.1186/s12989-019-0323-3. View

Zhang Q, Kleeberger S, Reddy S . DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung. Am J Physiol Lung Cell Mol Physiol. 2003; 286(2):L427-36. DOI: 10.1152/ajplung.00221.2003. View

Lovik M, Hogseth A, Gaarder P, Hagemann R, Eide I . Diesel exhaust particles and carbon black have adjuvant activity on the local lymph node response and systemic IgE production to ovalbumin. Toxicology. 1997; 121(2):165-78. DOI: 10.1016/s0300-483x(97)00075-9. View

Nordling E, Berglind N, Melen E, Emenius G, Hallberg J, Nyberg F . Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Epidemiology. 2008; 19(3):401-8. DOI: 10.1097/EDE.0b013e31816a1ce3. View

Takenaka S, Karg E, Kreyling W, Lentner B, Moller W, Behnke-Semmler M . Distribution pattern of inhaled ultrafine gold particles in the rat lung. Inhal Toxicol. 2006; 18(10):733-40. DOI: 10.1080/08958370600748281. View

Raleigh D, Marchiando A, Zhang Y, Shen L, Sasaki H, Wang Y . Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell. 2010; 21(7):1200-13. PMC: 2847524. DOI: 10.1091/mbc.e09-08-0734. View

Lehmann A, Blank F, Baum O, Gehr P, Rothen-Rutishauser B . Diesel exhaust particles modulate the tight junction protein occludin in lung cells in vitro. Part Fibre Toxicol. 2009; 6:26. PMC: 2770470. DOI: 10.1186/1743-8977-6-26. View

Tsukita S, Furuse M, Itoh M . Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001; 2(4):285-93. DOI: 10.1038/35067088. View

10.

Holder A, Goth-Goldstein R, Lucas D, Koshland C . Particle-induced artifacts in the MTT and LDH viability assays. Chem Res Toxicol. 2012; 25(9):1885-92. PMC: 3446248. DOI: 10.1021/tx3001708. View

11.

Pozarska A, Rodriguez-Castillo J, Surate Solaligue D, Ntokou A, Rath P, Mizikova I . Stereological monitoring of mouse lung alveolarization from the early postnatal period to adulthood. Am J Physiol Lung Cell Mol Physiol. 2017; 312(6):L882-L895. DOI: 10.1152/ajplung.00492.2016. View

12.

Laden F, Schwartz J, Speizer F, Dockery D . Reduction in fine particulate air pollution and mortality: Extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med. 2006; 173(6):667-72. PMC: 2662950. DOI: 10.1164/rccm.200503-443OC. View

13.

Staehelin L . Further observations on the fine structure of freeze-cleaved tight junctions. J Cell Sci. 1973; 13(3):763-86. DOI: 10.1242/jcs.13.3.763. View

14.

de Barros Mendes Lopes T, Groth E, Veras M, Furuya T, de Souza Xavier Costa N, Junior G . Pre- and postnatal exposure of mice to concentrated urban PM decreases the number of alveoli and leads to altered lung function at an early stage of life. Environ Pollut. 2018; 241:511-520. PMC: 6407120. DOI: 10.1016/j.envpol.2018.05.055. View

15.

Perez-Moreno M, Jamora C, Fuchs E . Sticky business: orchestrating cellular signals at adherens junctions. Cell. 2003; 112(4):535-48. DOI: 10.1016/s0092-8674(03)00108-9. View

16.

Gehring U, Wijga A, Hoek G, Bellander T, Berdel D, Bruske I . Exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence: a population-based birth cohort study. Lancet Respir Med. 2016; 3(12):933-42. DOI: 10.1016/S2213-2600(15)00426-9. View

17.

Shen L, Weber C, Raleigh D, Yu D, Turner J . Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol. 2010; 73:283-309. PMC: 4655434. DOI: 10.1146/annurev-physiol-012110-142150. View

18.

Dong C, Yin X, Ma J, Millecchia L, Wu Z, Barger M . Effect of diesel exhaust particles on allergic reactions and airway responsiveness in ovalbumin-sensitized brown Norway rats. Toxicol Sci. 2005; 88(1):202-12. DOI: 10.1093/toxsci/kfi280. View

19.

Hackett T, de Bruin H, Shaheen F, van den Berge M, Van Oosterhout A, Postma D . Caveolin-1 controls airway epithelial barrier function. Implications for asthma. Am J Respir Cell Mol Biol. 2013; 49(4):662-71. DOI: 10.1165/rcmb.2013-0124OC. View

20.

Li M, Fan L, Mao B, Yang J, Choi A, Cao W . Short-term Exposure to Ambient Fine Particulate Matter Increases Hospitalizations and Mortality in COPD: A Systematic Review and Meta-analysis. Chest. 2015; 149(2):447-458. DOI: 10.1378/chest.15-0513. View