Assessment of wood smoke induced pulmonary toxicity using bronchial, chronic bronchitis-like, and alveolar lung mucosa models at air-liquid interface
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ABSTRACT:
PROVIDER: PRJNA992532 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25195852_1.fastq.gz | Fastqsanger.gz | |||
| SRR25195852_2.fastq.gz | Fastqsanger.gz | |||
| SRR25195853_1.fastq.gz | Fastqsanger.gz | |||
| SRR25195853_2.fastq.gz | Fastqsanger.gz | |||
| SRR25195854_1.fastq.gz | Fastqsanger.gz |
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Project description: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. 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 minutes/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. 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.
2024-01-08 | GSE236857 | GEO
Project description:BackgroundChronic 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.MethodsThe 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.Results147 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.ConclusionFindings 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.
| S-EPMC10799428 | biostudies-literature
Project description:Heated tobacco products (HTP) are novel nicotine delivery products with limited toxicological data. HTP uses heating instead of combustion to generate aerosol (HTP-smoke). Physiologically relevant human bronchial and alveolar lung mucosa models developed at air-liquid interface were exposed to HTP-smoke to assess broad toxicological response (n=6-7; ISO puffing regimen; compared to sham; non-parametric statistical analysis; significance: p<0.05). Elevated levels of total cellular reactive oxygen species, stress responsive nuclear factor kappa-B, and DNA damage markers [8-hydroxy-2΄-deoxyguanosine, phosphorylated histone H2AX, cleaved poly-(ADP-Ribose) polymerase] were detected in HTP-smoke exposed bronchial and/ or alveolar models. RNA sequencing detected differential regulation of 724 genes in the bronchial- and 121 genes in the alveolar model following HTP-smoke exposure (cut off: p≤0.01; fold change: ≥2). Common enriched pathways included estrogen biosynthesis, ferroptosis, superoxide radical degradation, xenobiotics, and α-tocopherol degradation. Secreted levels of interleukin (IL)1ꞵ and IL8 increased in the bronchial model whereas in the alveolar model, interferon-γ and IL4 increased and IL13 decreased following HTP-smoke exposure. Increased lipid peroxidation was detected in HTP-smoke exposed bronchial and alveolar models which was inhibited by ferrostatin-1. The findings form a basis to perform independent risk assessment studies on different flavours of HTP using different puffing topography and corresponding chemical characterization.
2022-09-16 | GSE198082 | GEO
Project description:Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly, the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures.
2011-08-31 | GSE30660 | GEO
Project description:The Air Liquid Interface Model of Gastric Mucosa allows to provide a fully polarized epithelium accessible to infection experiments with H.pylori. The influence of several factors on immune response has been studied.
2018-02-15 | GSE94032 | GEO
Project description:Airway epithelial cells are the first cells of the lungs to be exposed to the toxic agents contained within cigarette smoke. Accordingly, the response of these cells to this challenge is of considerable interest in the context of diseases in which cigarette smoke is a major aetiological factor. We used Affymetrix microarrays to study the effects of repeated cigarette smoke challenge on three-dimensional human lung airway epithelial cultures. We have used cultures from four individual donors, and compared the effects of repeated cigarette smoke challenge (30mins exposure on four separate days), with no challenge.
2011-08-30 | E-GEOD-30660 | biostudies-arrayexpress
Project description:The differentiated human airway epithelium consists of different cell types forming a polarized and pseudostratified epithelium. This is dramatically altered in chronic obstructive pulmonary disease (COPD), characterized by basal and goblet cell hyperplasia, and squamous cell metaplasia. The effect of cigarette smoke on human bronchial epithelial cell (HBEC) differentiation remains to be elucidated. We analysed whether cigarette smoke extract (CSE) affected primary (p)HBEC differentiation and function. pHBEC were differentiated at the air-liquid interface (ALI) and differentiation was quantified after 7, 14, 21, or 28 days by assessing acetylated tubulin, CC10, or MUC5AC for ciliated, Clara, or goblet cells, respectively. Exposure of differentiating pHBEC to CSE impaired epithelial barrier formation, as assessed by resistance measurements (TEER). Importantly, CSE exposure significantly reduced the number of ciliated cells, while it increased the number of Clara and goblet cells. CSE-dependent cell number changes were reflected by a reduction of acetylated tubulin levels, an increased expression of the basal cell marker KRT14, and increased secretion of CC10, but not by changes in transcript levels of CC10, MUC5AC, or FOXJ1. Our data demonstrate that cigarette smoke specifically alters the cellular composition of the airway epithelium by affecting basal cell differentiation in a post-transcriptional manner.
| S-EPMC4313097 | biostudies-literature
Project description:We performed microarray analysis of miRNA expression in differentiating primary human bronchial epithelial cells. The goal was to identify miRNAs that are dynamically expressed under airway epithelial development. Cells were cultured at air-liquid-interface and were harvested day 4, 6, 8, 11, 13, 15, 18, 20 and 22 for analysis.
2021-01-09 | GSE164448 | GEO
Project description:Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality due to harmful effects mainly on the cardiovascular and respiratory system. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds. Although some critical pollutants, foremost particulate matter (PM), could be linked to adverse health effects, a comprehensive understanding of relevant biological mechanisms and detrimental aerosol constituents is still lacking. Here, we employed a systems toxicology approach focusing on wood combustion, an important source for air pollution, and demonstrate a key role of the gas phase, specifically carbonyls, to drive adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air-liquid-interface determined the DNA damage and stress response as well as perturbation of cellular metabolism as major key events. Connectivity mapping revealed a high similarity of gene expression signatures induced by wood smoke and agents prompting DNA-protein crosslinks (DPCs). Indeed, various gaseous aldehydes were detected in wood smoke, which promote DPCs, initiate similar genomic responses and are responsible for DNA damage provoked by wood smoke. Hence, systems toxicology enables the discovery of critical constituents of complex mixtures i.e. aerosols and highlights the role of carbonyls on top of particulate matter as important health hazard.
2023-09-01 | GSE228624 | GEO
Project description:Cigarette smoke (CS) is the leading cause to develop COPD. Therefore, we investigated the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC), from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions. The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity. Although, COPD-derived ALI cultures preserved some features known from COPD patients, the CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls. A RNA sequencing analysis revealed the deregulation for marker genes for basal cells and secretory cells upon CS exposure. The comparison between gene signatures obtained from our in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) reveals a high degree of similarity between the deregulated genes and pathways. ALI culture has been generated utilising cells obtained from 3 COPD and 3 healthy subjects. Subsequently cultures have been treated with CS and air respectively for 33 days. Gene expression profiles were generated using next generation sequencing.
2019-12-31 | GSE135188 | GEO