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Upadhyay, S.* ; Rahman, M.* ; Rinaldi, S.* ; Koelmel, J.P.* ; Lin, E.Z.* ; Mahesh, P.A.* ; Beckers, J. ; Johanson, G.* ; Pollitt, K.J.G.* ; Palmberg, L.* ; Irmler, M. ; Ganguly, K.*

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

Respir. Res. 25:49 (2024)
Verlagsversion DOI PMC
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Air Pollution ; Asthma ; Biomass ; Copd ; Cilia ; Ciliogenesis ; Hap ; Household ; Indoor ; Sdg; Wearable Passive Samplers; Biomass Smoke; Organic-compounds; Exposure; Secondary; Identification; Particles; Emissions; Pollution; Disease
ISSN (print) / ISBN 1465-9921
e-ISSN 1465-993X
Zeitschrift Respiratory Research
Quellenangaben Band: 25, Heft: 1, Seiten: , Artikelnummer: 49 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Förderungen Swedish Fund for Research without Animal Experiments
Swedish Heart Lung Foundation
Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Swedish Research Council
Karolinska Institute