Abstract
Exposure to urban particulate matter (UPM) is a high-risk factor for various ocular surface diseases, including dry eye syndrome. However, the effects of UPM on corneal and conjunctival epithelium damage have not been fully elucidated. In this study, we investigated the toxicological effects of UPM exposure at high concentrations by using in vitro cultures. The cell viability, mucin expression, and the secreted inflammatory mediators of corneal and conjunctival epithelial cells was observed at 24 h after exposure to UPM. The progression of cell cycle was also examined by flow cytometry at 24 h after exposure to UPM. UPM reduced cell viability in a dose-dependent manner and increased cell population in S and G2 phase. The expression of mucin-1 was attenuated by UPM exposure, but that of mucin-4 was not. UPM increased interleukin (IL)-6 release and decreased IL-8 release. The intensity of 2′,7′-dichlorofluorescein diacetate (DCF-DA) was highest at 4 h of UPM exposure. In conclusion, these results suggest that UPM causes the disruption of corneal and conjunctival epithelium by decreasing cell viability, altering cell cycle, disrupting mucin, and regulating inflammatory mediators.
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Abbreviations
- CCCk-8:
-
Cell Counting Kit-8
- DES:
-
Dry eye syndrome
- DEP:
-
Diesel exhaust particles
- ELISA:
-
Enzyme-linked immunosorbent assay
- IL:
-
Interleukin
- nitro-PAHs:
-
Nitro-substituted polycyclic aromatic hydrocarbons
- PAHs:
-
Polycyclic aromatic hydrocarbons
- PCB:
-
Polychlorinated biphenyl
- ROS:
-
Reactive oxygen species
- UPM:
-
Urban particulate matter
- WHO:
-
World Health Organization
References
Janine AS, Julie A, Carolyn B, Barbara C, Kelly N, Debra S, Oliver S (2007) The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye Work Shop. Ocul Surf 5:93–107
Michael AL, Christophe B, Jules B, Murat D, Gary NF, Shigeru K, Peter L, James M, Juan M, Stephen CP, Maurizio R, Ikuko T (2007) The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Work Shop. Ocul Surf 5:75–92
Jung SJ, Mehta JS, Tong L (2018) Effects of environment pollution on the ocular surface. Ocul Surf 16:198–205
Tau J, Novaes P, Matsuda M, Tasat DR, Saldiva PH, Berra A (2013) Diesel exhaust particles selectively induce both proinflammatory cytokines and mucin production in cornea and conjunctiva human cell lines. Invest Ophthalmol Vis Sci 54:4759–4765
IARC (2015) Outdoor air pollution. World Health Organization International Agency for Research on Cancer, Lyon
Aphekom (2011) Summary report of the Aphekom project 2008–2011. Aphekom, Saint-Maurice
Han C, Kim S, Lim YH, Bae HJ, Hong YC (2018) Spatial and temporal trends of number of deaths attributable to ambient PM2.5 in the Korea. J Korean Med Sci 33:e193
Chen IC, Huang HH, Chen PF, Chiang HC (2016) Sirtuin 3 protects against urban particulate matter-induced autophagy in human bronchial epithelial cells. Toxicol Sci 152:113–127
Huang YC, Li Z, Harder SD, Soukup JM (2004) Apoptotic and inflammatory effects induced by different particles in human alveolar macrophages. Inhal Toxicol 16:863–878
Soukup JM, Becker S (2001) Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin. Toxicol Appl Pharmacol 171:20–26
Obot CJ, Morandi MT, Beebe TP, Hamilton RF, Holian A (2002) Surface components of airborne particulate matter induce macrophage apoptosis through scavenger receptors. Toxicol Appl Pharmacol 184:98–106
Huggins FE, Huffman GP, Robertson JD (2000) Speciation of elements in NIST particulate matter SRMs 1648 and 1650. J Hazard Mater 74:1–23
Li J, Tan G, Ding X, Wang Y, Wu A, Yang Q, Ye L, Shao Y (2017) A mouse dry eye model induced by topical administration of the air pollutant particulate matter 10. Biomed Pharmacother 96:524–534
Jia YY, Wang Q, Liu T (2017) Toxicity research of PM2.5 compositions in vitro. Int J Environ Res Public Health 14:232
Hyun SW, Kim J, Park B, Jo K, Lee TG, Kim JS, Kim CS (2019) Apricot kernel extract and amygdalin inhibit urban particulate matter-induced keratoconjunctivitis sicca. Molecules 24:650
**ang P, He RW, Han YH, Sun HJ, Cui XY, Ma LQ (2016) Mechanisms of housedust-induced toxicity in primary human corneal epithelial cells: oxidative stress, proinflammatory response and mitochondrial dysfunction. Environ Int 89–90:30–37
Torricelli AA, Matsuda M, Novaes P, Braga AL, Saldiva PH, Alves MR, Monteiro ML (2014) Effects of ambient levels of traffic-derived air pollution on the ocular surface: analysis of symptoms, conjunctival goblet cell count and mucin 5AC gene expression. Environ Res 131:59–63
Kim YH, Oh TW, Park E, Yim NH, Park KI, Cho WK, Ma JY (2018) Anti-inflammatory and anti-apoptotic effects of acer palmatum thumb. Extract, KIOM-2015EW, in a hyperosmolar-stress-induced in vitro dry eye model. Nutrients 10:282
Longhin E, Holme JA, Gutzkow KB, Arlt VM, Kucab JE, Camatini M, Gualtieri M (2013) Cell cycle alterations induced by urban PM2.5 in bronchial epithelial cells: characterization of the process and possible mechanisms involved. Part Fibre Toxicol 10:63
Lin Z, Liu X, Zhou T, Wang Y, Bai L, He H, Liu Z (2011) A mouse dry eye model induced by topical administration of benzalkonium chloride. Mol Vis 17:257–264
Yoon S, Han S, Jeon KJ, Kwon S (2018) Effects of collected road dusts on cell viability, inflammatory response, and oxidative stress in cultured human corneal epithelial cells. Toxicol Lett 284:152–160
Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter RM (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801
Novaes P, Do Nascimento Saldiva PH, Kara-Jose N, Macchione M, Matsuda M, Racca L, Berra A (2007) Ambient levels of air pollution induce goblet-cell hyperplasia in human conjunctival epithelium. Environ Health Perspect 115:1753–1756
Gipson IK, Spurr-Michaud SJ, Senchyna M, Ritter R 3rd, Schaumberg D (2011) Comparison of mucin levels at the ocular surface of postmenopausal women with and without a history of dry eye. Cornea 30:1346–1352
Enriquez-de-Salamanca A, Bonini S, Calonge M (2012) Molecular and cellular biomarkers in dry eye disease and ocular allergy. Curr Opin Allergy Clin Immunol 12:523–533
Corrales RM, Narayanan S, Fernandez I, Mayo A, Galarreta DJ, Fuentes-Paez G, Chaves FJ, Herreras JM, Calonge M (2011) Ocular mucin gene expression levels as biomarkers for the diagnosis of dry eye syndrome. Invest Ophthalmol Vis Sci 52:8363–8369
Albertsmeyer AC, Kakkassery V, Spurr-Michaud S, Beeks O, Gipson IK (2010) Effect of pro-inflammatory mediators on membrane-associated mucins expressed by human ocular surface epithelial cells. Exp Eye Res 90:444–451
Ablamowicz AF, Nichols JJ (2016) Ocular surface membrane-associated mucins. Ocul Surf 14:331–341
Johnson ME, Murphy PJ (2004) Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 23:449–474
Imbert Y, Darling DS, Jumblatt MM, Foulks GN, Couzin EG, Steele PS, Young Jr. WW (2006) MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls. Exp Eye Res 83:493–501
Berry M, Pult H, Purslow C, Murphy PJ (2008) Mucins and ocular signs in symptomatic and asymptomatic contact lens wear. Optom Vis Sci 85:E930–E938
Wang IJ, Wu CY, Hu FR (2007) Effect of proinflammatory cytokines on the human MUC5AC promoter activity in vitro and in vivo. Clin Ophthalmol 1:71–77
** SP, Li Z, Choi EK, Lee S, Kim YK, Seo EY, Chung JH, Cho S (2018) Urban particulate matter in air pollution penetrates into the barrier-disrupted skin and produces ROS-dependent cutaneous inflammatory response in vivo. J Dermatol Sci 91:175–183
Fu Q, Lyu D, Zhang L, Qin Z, Tang Q, Yin H, Lou X, Chen Z, Yao K (2017) Airborne particulate matter (PM2.5) triggers autophagy in human corneal epithelial cell line. Environ Pollut 227:314–322
Acknowledgements
This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (#317033-03). This work was also supported by Korea Institute of Oriental Medicine (Project No. KSN1812080) and NST (National Research Council of Science & Technology)-KIOM (Korea Institute of Oriental Medicine) Postdoctoral Research Fellowship for Young Scientists.
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Hyun, SW., Song, S.J., Park, B. et al. Toxicological effects of urban particulate matter on corneal and conjunctival epithelial cells. Toxicol Res. 36, 311–318 (2020). https://doi.org/10.1007/s43188-019-00034-0
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DOI: https://doi.org/10.1007/s43188-019-00034-0