Assessment of wood smoke induced pulmonary toxicity in normal- and chronic bronchitis-like bronchial and alveolar lung mucosa models at air-liquid interface.

Autor: Upadhyay S; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden. swapna.upadhyay@ki.se., Rahman M; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden., Rinaldi S; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden., Koelmel J; Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA., Lin EZ; Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA., Mahesh PA; Department of Respiratory Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, 570015, India., Beckers J; Institute of Experimental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum Für Gesundheit Und Umwelt (GmbH), 85764, Neuherberg, Germany.; German Center for Diabetes Research (DZD E.V.), 85764, Neuherberg, Germany.; Chair of Experimental Genetics, Technical University of Munich, 85354, Freising, Germany., Johanson G; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden., Pollitt KJG; Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA., Palmberg L; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden., Irmler M; Institute of Experimental Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum Für Gesundheit Und Umwelt (GmbH), 85764, Neuherberg, Germany., Ganguly K; Unit of Integrative Toxicology, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77, Stockholm, Sweden. koustav.ganguly@ki.se.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2024 Jan 20; Vol. 25 (1), pp. 49. Date of Electronic Publication: 2024 Jan 20.
DOI: 10.1186/s12931-024-02686-5
Abstrakt: Background: Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air-liquid interface (ALI) to assess broad toxicological end points.
Methods: The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 min/exposure; 5-exposures over 3-days; n = 6-7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p ≤ 0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed.
Results: 147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the 'cilium' related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p < 0.05) in WS-exposed bro-ALI and bro-ALI-CB.
Conclusion: Findings of this study indicate differential response to WS-exposure in different lung regions and in chronic bronchitis, a condition commonly associated with COPD. Further, the data suggests ciliopathy as a candidate pathway in relation to WS-exposure.
(© 2024. The Author(s).)
Databáze: MEDLINE
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