Repeated Exposure to Wood Smoke Alters Pulmonary Gene and Metabolic Profiles
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE237251 | GEO | 2024/06/05
REPOSITORIES: GEO
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Project description:Increase in frequency and size of wildfire raises a significant public health concern due to rapid climate change. Epidemiological studies have shown that wildfire smoke exposure can increase the risk of neurological disorders. Our study aims to understand how wildfire smoke particles affect brain endothelial cells using both primary human brain microvascular endothelial cells (HBMEC) and an immortalized human cerebral microvascular endothelial cell line (hCMEC/D3). HBMEC and hCMEC/D3 were exposed to different levels of smoldering eucalyptus smoke particles (10, 30, 50 ug/mL) for 24 hr. Supernatants were collected for LDH and ELISA array, cell lysates were collected for RNAseq, and cells were fixed and stained for tight junction marker (Zonula Occludens-1, ZO-1) via ICC. Our study found that treatment to smoldering eucalyptus particles can increase inflammatory cytokine production dose-dependently in HBMECs and hCMEC/D3. Moreover, RNAseq analyses resulted in dose-dependent changes in HBMEC and hCMEC/D3 from wood smoke treatment that could be mediated via AhR and Nrf2 pathways.
2024-10-02 | GSE271935 | GEO
Project description:Repeated Exposure to Wood Smoke Alters Pulmonary Gene and Metabolic Profiles
| PRJNA994474 | ENA
Project description:Transcriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.
2021-02-24 | GSE167371 | GEO
Project description:Transcriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.
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Project description:Exposure to cigarette smoke (CS) is etiologically linked to the development of fatal respiratory diseases, and there is a need to understand the mechanisms whereby CS causes damage. While animal models have provided valuable insights into smoking-related respiratory tract damage, modern toxicity testing calls for reliable in vitro models as alternatives for animal experimentation. Primary cells and immortalized cell lines can be used to gain some insight; however, the three-dimensional organotypic culture systems probably better mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Even though the bronchus, bronchioles, and lung parenchyma are the primary sites of smoking-related respiratory disease manifestation, the nasal epithelium has been proposed as a surrogate tissue to study the effects of smoking on the respiratory tract. Here, we report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures from which transcriptomic data were collected at several post-exposure time points. Despite the remarkably similar histology and cellular response to whole CS in both tissue types, as measured by cellular staining and cytokine secretion assessment, transcriptomic analyses combined with quantitative biological network modeling identified biological mechanisms that were unique to bronchial tissue at late post-exposure time points. Organotypic models therefore appear to be a promising alternative to animal experimentation, and provide species-relevant insights into the effects of CS exposure on the respiratory system.
2014-09-30 | E-MTAB-2250 | biostudies-arrayexpress
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2023-11-13 | PXD046918 |
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