Abstract
Exposure to diesel exhaust particles (DEPs) and urban particles (UPs) increases the incidence of degenerative brain diseases as well as respiratory diseases. However, there is limited evidence on the mechanism of neurotoxicity on exposure to these particles. In the present study, the damage to blood–brain barrier (BBB) function by DEP or UP exposure was evaluated in bEnd.3 cells, which are derived from the brain tissue of Balb/c mice. It was demonstrated that DEP and UP exposure may induce oxidative stress via increasing reactive oxygen species (ROS) and decreasing total antioxidant capacity (TAC) level in bEnd.3 cells. In addition, cells exposed to DEP and UP demonstrated a resistance value of about 50% each compared to the value noted prior to exposure; additionally, Claudin-5 and ZO-1 expression levels were significantly decreased compared to the corresponding levels in the control. It was inferred that DEP or UP exposure diminishes the expression of tight junction proteins in endothelial cells through ROS generation, thereby enhancing endothelial membrane permeability. This study showed that DEPs or UPs induced cell permeability and oxidative stress by increasing ROS generation in bEnd.3 cells. This suggests the possibility that exposure to DEPs or UPs may compromise the integrity of the BBB and induce adverse effects in the CNS.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs43188-021-00110-4/MediaObjects/43188_2021_110_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs43188-021-00110-4/MediaObjects/43188_2021_110_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs43188-021-00110-4/MediaObjects/43188_2021_110_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs43188-021-00110-4/MediaObjects/43188_2021_110_Fig4_HTML.png)
Similar content being viewed by others
References
Peters A, Beronesi B, Garciduenas LC, Gehr P, Chen LC, Geiser M, Reed W, Rutishauser BR, Schurch S, Schulz H (2006) Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part Fiber Toxicol 3:13. https://doi.org/10.1186/1743-8977-3-13
Bunn WB 3rd, Hesterberg TW, Valberg PA, Slavin TJ, Hart G, Lapin CA (2004) A reevaluation of the literature regarding the health assessment of diesel engine exhaust. Inhal Toxicol 16:889–900. https://doi.org/10.1080/08958370490883783
Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC Jr, Tager I (2004) Air pollution and cardiovascular disease—a statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109:2655–2671. https://doi.org/10.1161/01.CIR.0000128587.30041.C8
Pope CA, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA J Am Med Assoc 287:1132–1141. https://doi.org/10.1001/jama.287.9.1132
Hartz AMS, Bauer B, Block ML, Hong JS, Miller DS (2008) Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier. Faseb J 22:2723–2733. https://doi.org/10.1096/fj.08-106997
Kleinman MT, Araujo JA, Nel A, Siotas C, Campbell A, Cong PQ, Li H, Bondy SC (2008) Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways. Toxicol Lett 178:127–130. https://doi.org/10.1016/j.toxlet.2008.03.001
Block ML, Wu X, Pei Z, Li G, Wang T, Qin L, Wilson B, Yang J, Hong S, Veronesi B (2004) Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase. FASEB J 18:1618. https://doi.org/10.1096/fj.04-1945fje
Sawyer K, Mundandhara S, Ghio AJ, Madden MC (2010) The effects of ambient particulate matter on human alveolar macrophage oxidative and inflammatory responses. J Toxicol Environ Heal A 73:41–57. https://doi.org/10.1080/15287390903248901
Tal TL, Simmons SO, Silbajoris R, Daily L, Cho SH, Ramabhadran R, Linak W, Reed W, Bromberg PA, Samet JM (2010) Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles. Toxicol Appl Pharmacol 243:46–54. https://doi.org/10.1016/j.taap.2009.11.011
Kim YD, Lanz-McPeak SM, Ali SF, Kleinman MT, Choi YS, Kim H (2014) Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells. Environ Toxicol Pharmacol 37:954–959. https://doi.org/10.1016/j.etap.2014.03.008
Jiang H, Shen YM, Quinn AM, Penning TM (2005) Competing roles of cytochrome P450 1A1/1B1 and aldo-keto reductase 1A1 in the metabolic activation of (+/−)-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene in human bronchoalveolar cell extracts. Chem Res Toxicol 18:365–374. https://doi.org/10.1021/tx0497245
FlowersGeary L, Bleczinski W, Harvey RG, Penning TM (1996) Cytotoxicity and mutagenicity of polycyclic aromatic hydrocarbon o-quinones produced by dihydrodiol dehydrogenase. Chem Biol Interact 99:55–72. https://doi.org/10.1016/0009-2797(95)03660-1
Bolton SJ, Anthony DC, Perry VH (1998) Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86:1245–1257. https://doi.org/10.1016/S0306-4522(98)00058-X
Weiss N, Miller F, Cazaubon S, Couraud PO (2009) The blood-brain barrier in brain homeostasis and neurological diseases. BBA-Biomembr 1788:842–857. https://doi.org/10.1016/j.bbamem.2008.10.022
Jiao H, Wang Z, Liu Y, Wang P, Xue Y (2011) Specific role of tight junction proteins claudin-5, occludin, and ZO-1 of the blood–brain barrier in a focal cerebral ischemic insult. J Mol Neurosci 44:130–139. https://doi.org/10.1007/s12031-011-9496-4
Choi YS, Eom SY, Kim IS, Ali SF, Kleinman MT, Kim YD, Kim H (2016) Fucoidan extracted from Hijiki protects brain microvessel endothelial cells against diesel exhaust particle exposure-induced disruption. J Med Food 19:466–471. https://doi.org/10.1089/jmf.2015.3635
Choi YS, Eom SY, Park H, Ali SF, Lanz-McPeak KMT, Kim YD, Kim H (2014) Toxicity of low doses of ultrafine diesel exhaust particles on bovine brain microvessel endothelial cells. Mol Cell Toxicol 10:245–250. https://doi.org/10.1007/s13273-014-0027-6
Helms HC, Abbott NJ, Burek M, Cecchelli R, Couraud PO, Deli MA, Forster C, Galla HJ, Romero IA, Shusta EV, Stebbins M, Vandenhaute E, Weksler B, Brodin B (2016) In vitro models of the blood–brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab 36:862–890. https://doi.org/10.1177/0271678X16630991
Voirin AC, Perek N, Roche F (2020) Inflammatory stress induced by a combination of cytokines (IL-6, IL-17, TNF-α) leads to a loss of integrity on bEnd.3 endothelial cells in vitro BBB model. Brain Res 1730:146647. https://doi.org/10.1016/j.brainres.2020.146647
Jung YS, Kim CS, Park HS, Sohn S, Lee BH, Moon CK, Lee SH, Baik EJ, Moon CH (2003) N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells (bEnd.3). J Pharmacol Sci 93:489–495. https://doi.org/10.1254/jphs.93.489
Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radical Bio Med 27:612–616. https://doi.org/10.1016/S0891-5849(99)00107-0
Apak R, Guclu K, Demirata B, Ozyurek M, Celik SE, Bektasoglu B, Berker KI, Ozyurt D (2007) Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules 12:1496–1547. https://doi.org/10.3390/12071496
Al-Sadi R, Guo S, Ye D, Dokladny K, Alhmoud T, Ereifej L, Said HM, Ma TY (2013) Mechanism of IL-1b modulation of intestinal epithelial barrier involves p38 kinase and activating transcription factor-2 activation. J Immunol 190:6596–6606. https://doi.org/10.4049/jimmunol.1201876
Burtscher H, Schuepp K (2012) The occurrence of ultrafine particles in the specific environment of children. Paediatr Respir Rev 13:89–94. https://doi.org/10.1016/j.prrv.2011.07.004
Levesque S, Surace MJ, McDonald J, Block ML (2011) Air pollution and the brain: subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease. J Neuroinflamm 8:105. https://doi.org/10.1186/1742-2094-8-105
Vuong TT, Ronning SB, Suso HP, Schmidt R, Prydz K, Lundstrom M, Moen A, Pedersen ME (2017) The extracellular matrix of eggshell displays anti-inflammatory activities through NF-κB in LPS-triggered human immune cells. J Inflamm Res 10:83–96. https://doi.org/10.2147/jir.s130974
Acknowledgements
This work was supported by the National Research Foundation of Korea grant funded by the Korea government (MSIT) (2016R1A2B4011280). We thank its funding.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JYK, SH and OB. The first draft of the manuscript was written by Y-DK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Kim, J.Y., Hong, S., Bolormaa, O. et al. Effects of diesel exhaust particles and urban particles on brain endothelial cells. Toxicol Res. 38, 91–98 (2022). https://doi.org/10.1007/s43188-021-00110-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43188-021-00110-4