Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models

Eunsook Park; Bu-Yeo Kim; Seahyoung Lee; Kuk Hui Son; Jihye Bang; Se Hyang Hong; Joong Won Lee; Kyung-Ok Uhm; Hyun-Jeong Kwak; Hyun Joung Lim

doi:10.1016/j.ecoenv.2024.116090

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models

Ecotoxicol Environ Saf. 2024 Mar 15:273:116090. doi: 10.1016/j.ecoenv.2024.116090. Epub 2024 Feb 15.

Authors

Affiliations

¹ Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Chungju, Chungcheongbuk-do 28159, South Korea.
² Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
³ Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea.
⁴ Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon 215565, South Korea.
⁵ Department of Bio and Fermentation Convergence Technology, Kookmin Univerisity, Seonbuk-Gu, Seoul 02707, South Korea.
⁶ Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Chungju, Chungcheongbuk-do 28159, South Korea. Electronic address: hjlim1121@korea.kr.

PMID: 38364346
DOI: 10.1016/j.ecoenv.2024.116090

Abstract

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM_2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM_2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM_2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1β, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Keywords: Air-liquid interface; Ciliary function; Diesel exhaust particle; Mucociliary clearance; Normal human bronchial epithelial cell.

MeSH terms

Epithelial Cells
Epithelium
Humans
Lung Injury* / metabolism
Particulate Matter / metabolism
Respiratory Mucosa
Vehicle Emissions* / toxicity

Substances

Vehicle Emissions
Particulate Matter