ScRNA-seq of lung cells from murine model of ozone induced asthma exacerbation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE285723 | GEO | 2025/12/02
REPOSITORIES: GEO
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Project description:In this study, integrated transcriptomics, proteomics and metabolomics approaches were applied to investigate the molecular responses of O3 in the leaves of two-weeks old rice (cv. Nipponbare) seedlings exposed to 0.2 ppm O3 for a period of 24 h. Based on the morphological alteration of O3-exposed rice leaves, transcript profiling of rice genes was performed in leaves exposed for 1, 12 and 24 h using rice DNA microarray chip, proteomics and metabolomics. This systematic survey showed that O3 triggers a chain reaction of altered gene, protein and metabolite expressions involved in multiple cellular processes in rice. Also investigated were the molecular responses in the leaves of two-weeks old rice (cv. Nipponbare) seedlings under continuous light and pure air (as a positive control for ozone exposure experiments) for a period of 24 h. Transcript profiling of rice genes was performed in leaves exposed for 1, 12 and 24 h using rice DNA microarray chip, proteomics and metabolomics. This systematic survey showed that continuous light and growth for 24 h also triggers a chain reaction of altered gene expressions involved in multiple cellular processes in rice, but different from those against ozone, in general. Keywords: Ozone fumigation response
2008-04-24 | GSE11157 | GEO
Project description:Obese mice have an augmented response to Ozone exposure (2 ppm for 3 hours and studied 24 hours later), including increase airway hyperresponsiveness and BAL inflammation when compared to WT ozone exposed mice. When IL-17A is block with systemic injected of IL-17A antibodies there is a decrease of response in the obese mice. To determine the mechanism of action, RNA was extracted from the lungs of IL-17A and Isotype injected ozone exposed obese mice and microarray analysis of gene expression was performed.
2016-05-24 | GSE81800 | GEO
Project description:In this study, integrated transcriptomics, proteomics and metabolomics approaches were applied to investigate the molecular responses of O3 in the leaves of two-weeks old rice (cv. Nipponbare) seedlings exposed to 0.2 ppm O3 for a period of 24 h. Based on the morphological alteration of O3-exposed rice leaves, transcript profiling of rice genes was performed in leaves exposed for 1, 12 and 24 h using rice DNA microarray chip, proteomics and metabolomics. This systematic survey showed that O3 triggers a chain reaction of altered gene, protein and metabolite expressions involved in multiple cellular processes in rice. Also investigated were the molecular responses in the leaves of two-weeks old rice (cv. Nipponbare) seedlings under continuous light and pure air (as a positive control for ozone exposure experiments) for a period of 24 h. Transcript profiling of rice genes was performed in leaves exposed for 1, 12 and 24 h using rice DNA microarray chip, proteomics and metabolomics. This systematic survey showed that continuous light and growth for 24 h also triggers a chain reaction of altered gene expressions involved in multiple cellular processes in rice, but different from those against ozone, in general. Experiment Overall Design: Ozone-treated Samples: An in vivo 14-days-old rice seedling model system was used, where whole seedlings were used for exposure/fumigation to the ozone (0.2 ppm). Dye-swap or reverse labeling with Cy3 and Cy5 dyes procedure was applied followed by hybridization and wash processes, and the hybridized microarrays (G4138A) were scanned using a GenePix microarray scanner followed by the Gene Pix 4000 analysis application program for image analysis and data extraction processes. The GeneSpring Ver. 4 software was used for normalization. Experiment Overall Design: Control Samples: An in vivo 14-days-old rice seedling model system was used, where whole seedlings were used for exposure to continuous light and pure air. Dye-swap or reverse labeling with Cy3 and Cy5 dyes procedure was applied followed by hybridization and wash processes, and the hybridized microarrays (G4138A) were scanned using a Standard protocol of Agilent DNA Microarray Scanner and data processing was done by Feature Extraction software Version 8.1 from Agilent Technologies.
2008-06-11 | E-GEOD-11157 | biostudies-arrayexpress
Project description:Background: Ozone (O3) is the predominant oxidant air pollutant associated with respiratory inflammation, lung dysfunction, and worsening preexisting airway diseases. We determined that TNFR signlaing pathway plays a key role in lung injury and inflammation caused by O3 in mice. However, downstream molecular mechanisms underlying TNFR pathway have not been investigated. Methods: To investigate the role of TNFR pathway in gene expression changes, Tnfr1/2-deficient (Tnfr-/-) and wild-type (Tnfr+/+, C57BL/6J) mice were exposed to air or 0.3-ppm O3. Total RNAs were isolated from lung homogenates and cDNA microarray analyses were performed to elucidate TNFR-directed transcriptomics in basal lungs (air-exposed) as well as in the lung exposed to time course of O3 (24, 48, and 72 hr). Results: O3 caused time-dependent changes in lung gene expressions with the greatest transcriptome changes at 48-72 hr of exposure in Tnfr+/+ mice. At early time of exposure (24 hr), acute phase and inflammatory responses gene as well as redox and lipid metabolism genes were increased by O3 while cell cycle and DNA damage repair genes were markedly increased by O3 at later time points (48-72 hr). Compared to Tnfr+/+ mice, Tnfr-/- mice had lowered expression of inflammatory response and vascular disorder-related genes at baseline (air). After O3 exposure, Tnfr-/- had enhanced expression of immune and inflammatory genes at 24 hr, indicating compensatory or adpative poentiation of immunity in Tnfr-/- mice. At 48 hr of O3 exposure, Tnfr-/- mice showed suppressed expression of genes involved in epithelial proliferation, inflammatory cell influxes and epithelial injury, compared to Tnfr+/+ mice. At 72 hr of O3 exposure, neurodegeneration and neurotransmitter transport genes were suppressed in Tnfr-/- than in Tnfr+/+. Conclusion: Overall, deficiency of TNFR-mediated signaling in mouse lungs altered transcriptomes to protect lungs from O3-induced inflammation, cell proliferation, oxidative stress, and neuronal disorders.
2021-09-29 | GSE166399 | GEO
Project description:Populus deltoides and Populus trichocarpa were exposed to either ambient air or an acute ozone exposure of 200 ppb for 9 hrs and ozone response was profiled for each genotype by hybridising control against ozone-exposed samples per genotype. Keywords: stress response, genotype comparrison, ozone exposure
2009-04-01 | GSE10874 | GEO
Project description:Background: Ozone (O3) is the predominant oxidant air pollutant associated with respiratory inflammation, lung dysfunction, and worsening preexisting airway diseases. We previously determined that lack of NF-kB signlaing pathway suppressed lung injury and inflammation caused by O3 in mice. The current study was to determine transcriptome mechanisms orchestrated by NF-kB during the development of pulmonary O3 injury. Methods: To investigate the role of NF-kB1 pathway in lung gene expression changes, Nfkb1-deficient (Nfkb1-/-) and wild-type (Nfkb1+/+) mice were exposed to air or 0.3-ppm O3. Total RNAs were isolated from lung homogenates and cDNA microarray analyses were performed to elucidate NF-kB1-directed transcriptomics in basal lungs (air-exposed) as well as in the lung exposed to O3 (48 hr). Results: In air-exposed Nfkb1-/- lungs, leukocyte extravasation/adhesion and antigen presentation genes were overexpressed while immunity genes were suppressed, supporting the dual role of Nf-kB1 homodimer as a transcriptional repressor as well as transcriptional activator and the phenotype of Nfkb1-/- mice (defective response to infection and specific antibody production). After O3 exposure. Nfkb1-/- mice showed suppressed expression of lung cell cycle genes and enhanced expression of DNA damage checkpoint regulation pathway genes, compared to Nfkb1+/+ mice. Conclusion: Overall, deficiency of NF-kB1 in mouse lungs altered transcriptomes to protect lungs from O3-induced inflammation, cell proliferation, and DNA damages.
2021-09-29 | GSE166398 | GEO
Project description:Ozone (O3) is a prevalent air pollutant that causes lung inflammation following exposure. Previous studies demonstrate that O3 oxidizes lipids, such as cholesterol, in the airway to produce oxidized cholesterol products (oxysterols), such as secosterol-A (secoA), which form covalent linkages preferentially with lysine residues and consequently modify protein function. The breadth of proteins modified by this oxysterol as well as the biological consequences in the lung are unknown. Using an alkynyl-tagged form of secosterol-A and shotgun proteomics, we identified NLR Family Pyrin Domain Containing 2 (NLRP2) to be adducted at lysine (K1019) in the terminal leucine-rich-repeat, a known regulatory region for NLR proteins. We characterized NLRP2 expression in airway epithelial cells and used CRISPR-Cas9 knockout and shRNA knockdown of NLRP2 for analysis of inflammasome complex activity and pro-inflammatory mediator production following O3 exposure. We observed an increase in caspase-1 activity in response to O3, which was not altered by knocked down NLRP2 expression. O3-induced pro-inflammatory gene expression for CXCL1, CXCL2, and IL8 was further enhanced in NLRP2 knockout cells. Together, our findings uncover NLRP2 as a highly abundant, key component of pro-inflammatory signaling pathways in airway epithelial cells and formation of oxysterol-NLRP2 adduct as a novel mediator of O3-induced inflammation.
2021-06-21 | PXD019824 | Pride
Project description:Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying IL-10-mediated attenuation of O3-induced pulmonary inflammation in mice. Methods: Il10-deficient (Il10-/-) and wild type (Il10+/+) mice were exposed to 0.3-ppm O3 or filtered air for 24, 48 or 72 hr. Immediately following exposure, differential cell counts, and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10-/- mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
2011-10-19 | GSE25095 | GEO
Project description:Long-term exposure to particulate air pollutants has been linked to increased incidence of Type 2 Diabetes (T2DM). Recently, we showed that the gaseous pollutant, O3, induced glucose intolerance, and increased serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause broad scale changes in metabolic homeostasis involving liver, muscle and adipose tissues, and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights into pollutant-induced metabolic alterations. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.00 ppm, 6h/day for two consecutive days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O3, 6h/day for either one day or two consecutive days and systemic metabolic responses were determined immediately after each exposure or after an 18h recovery period. In WKY rats, O3 increased serum fasting glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18h post second exposure. O3 exposure increased circulating metabolites of glycolysis, long-chain free fatty acids, branched chain amino acids (BCAA) and cholesterol while 1,5- anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, muscle proteolysis and adipose lipolysis. Liver gene expression profile after O3 exposure reflected a response to the serum metabolite changes, as evidenced by increased expression of genes for glycolysis, TCA cycle and gluconeogenesis, and decreased expression of genes involved in steroid and fat biosynthesis. In conclusion, short-term O3 exposure induced hormonal changes and global metabolic disorder reflective of changes in peripheral glucose, lipid, and amino acid metabolism, representative of a stress-response. It remains to be examined if these metabolic alterations contribute to insulin resistance upon chronic exposure. Rats were exposed to filtered air (FA) or Ozone at 1 ppm, 6h/day for two consecutive days to establish ozone-exposure related effects on transcriptomic profiles. Samples were taken at three time points: 1 day (1day0hrs) - at the end of the 6 hour exposure period, 2 days (2day0hrs) - at the end of the of the second day 6 hour exposure period) and 2 days 18 hours (2day18hrs) - 18 hours after the 6 hour exposure period on the second day. Total liver RNA was isolated from ~20 mg tissue with a commercially available RNeasy mini kit (Qiagen, Valencia, CA) using silica gel membrane purification. Liver RNA was resuspended in 30μl of RNAse- free water. RNAse inhibitor was added and RNA yield was determined spectrophotometrically on a NanoDrop 1000 (Thermo Scientific, Wilmington, DE). RNA integrity was assessed by the RNA 6000 LabChip® kit using a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). We examined global gene expression changes using the Affymetrix platform (RG- 230 PM Array strip). Biotin-labeled cRNA was produced from total RNA using an Affymetrix “IVT-express labeling kit “(cat# 901229).
2015-01-31 | E-GEOD-59329 | biostudies-arrayexpress
Project description:Background: The mechanisms underlying ozone (O3)-induced pulmonary inflammation remain unclear. Interleukin (IL)-10 is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: The current study investigated the molecular mechanisms underlying IL-10-mediated attenuation of O3-induced pulmonary inflammation in mice. Methods: Il10-deficient (Il10-/-) and wild type (Il10+/+) mice were exposed to 0.3-ppm O3 or filtered air for 24, 48 or 72 hr. Immediately following exposure, differential cell counts, and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also utilized global mRNA expression analyses of lung tissue with Ingenuity Pathway Analyses (IPA) to identify patterns of gene expression through which IL-10 modifies O3-induced inflammation. Results: Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10-/- mice than in Il10+/+ mice after exposure to O3 at all time points tested. O3-enhanced nuclear NF-kB translocation was elevated in the lungs of Il10-/- compared to Il10+/+ mice. Gene expression analyses revealed several key IL-10 and O3-dependent mediators, including IL-6, MIP-2, IL-1 and CD86. Conclusions: Results indicated that IL-10 protects against O3-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several novel genetic targets (e.g. Ccr1, Socs3, Il33, Hat1, and Gale) through which IL10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O3-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals. PARALLEL study design with 26 samples. Biological replicates: 2 to 3 replicates per group with wild type air exposed animals as controls for each time point (24, 48, 72 hours). Time-Course, Dose-Response, Strain comparison
2011-10-18 | E-GEOD-25095 | biostudies-arrayexpress