Homo sapiens
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PROVIDER: PRJNA108145 | ENA |
REPOSITORIES: ENA
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Project description:Exposure to particulate matter (PM) is consistently associated with increased morbidity and mortality attributable in part to respiratory illnesses. The alveolar macrophage (AM) is one of the cell types in the lung constantly exposed to and activated by ambient pollutants. Upon contact with environmental particulate pollutants, AM produces reactive oxygen species (ROS) and antioxidant enzymes, but the scope of this oxidative stress response induced by PM remains poorly defined. In this study, we used microarray analysis to determine the gene expression profile in human alveolar macrophages upon exposure to PM and sought to gain more insight into the global response of pro- and anti-oxidant enzymes to PM exposure. Human AM were obtained by bronchoscopy from normal individuals. They were then incubated with Chapel Hill PM2.5 (1 ïg/ml) or vehicle for 4 hours (n = 6 independent samples each). mRNAs were extracted, amplified and hybridized to Agilent Human 1A microarray. Differentially expressed genes were identified by Statistical Analysis for Microarrays (SAM) with a FDR of 10% and a P ⤠0.05. Significant genes were also mapped with Gene Ontology (GO) based on their molecular function. We found 34 and 41 up- and down-regulated genes respectively. Of these, 22 genes (~30%) were involved in metal binding and 14 genes were linked to oxidative stress, including 5 metallothionein-1 (MT1) isoform genes. In lung cells, addition of MT-1F in the medium attenuated PM2.5-induced H2O2 production while knockdown of MT1F gene expression increased H2O2 and IL-6 release induced by PM2.5. Our microarray experiments provided a global view of gene expression after in vitro PM2.5 exposure in human AM. The expression profile was most notable for differential expression of genes related to metal binding and oxidative stress, especially upregulation of MT1 isoform genes. Our findings suggest that metals associated with PM, e.g., zinc, copper, and arsenic, induce MT-1 and may be the primary mediators for PM-induced oxidative stress. Keywords: in vitro exposure, PM2.5 particle treatment, human alveolar macrophages Total RNA was isolated from alveolar macrophages from 6 subjects were treated in vitro with PM2.5 particles or vehicle control for 4 hrs. All particle-treated samples were co-hybridized with the common reference sample (pool of all 6 vehicle-treated samples) twice with Cy3 and Cy5 dyes flipped (12 hybridizations). Three samples were also co-hybridized with its own individual control (vehicle-treatment for the same subject) with Cy3 and Cy5 dyes flipped (6 additional hybridizations).
2008-05-01 | E-GEOD-10394 | biostudies-arrayexpress
Project description:The toxicity of silver and zinc oxide nanoparticles is hypothesised to be mediated by dissolved metal ions and cerium dioxide nanoparticles (CeO2 NPs) are hypothesised to induce toxicity specifically by oxidative stress dependant on their surface redox state. To test these hypotheses, RNAseq was applied to characterise the molecular responses of cells to metal nanoparticle and metal ion exposures. The human epithelial lung carcinoma cell line A549 was exposed to different CeO2 NPs with different surface charges, micron-sized and nano-sized silver particles and silver ions, micron-sized and nano-sized zinc oxide particles and zinc ions, or control conditions, for 1 hour, 6 hours and 24 hours. Concentrations were the lower of either EC20 or 128 micrograms/mL. Transcriptional responses were characterised by RNAseq transcriptomics using an Illumina HiSeq2500 .
2018-02-01 | E-MTAB-5734 | biostudies-arrayexpress
Project description:Exposure to particulate matter (PM) is consistently associated with increased morbidity and mortality attributable in part to respiratory illnesses. The alveolar macrophage (AM) is one of the cell types in the lung constantly exposed to and activated by ambient pollutants. Upon contact with environmental particulate pollutants, AM produces reactive oxygen species (ROS) and antioxidant enzymes, but the scope of this oxidative stress response induced by PM remains poorly defined. In this study, we used microarray analysis to determine the gene expression profile in human alveolar macrophages upon exposure to PM and sought to gain more insight into the global response of pro- and anti-oxidant enzymes to PM exposure. Human AM were obtained by bronchoscopy from normal individuals. They were then incubated with Chapel Hill PM2.5 (1 ug/ml) or vehicle for 4 hours (n = 6 independent samples each). mRNAs were extracted, amplified and hybridized to Agilent Human 1A microarray. Differentially expressed genes were identified by Statistical Analysis for Microarrays (SAM) with a FDR of 10% and a P ≤ 0.05. Significant genes were also mapped with Gene Ontology (GO) based on their molecular function. We found 34 and 41 up- and down-regulated genes respectively. Of these, 22 genes (~30%) were involved in metal binding and 14 genes were linked to oxidative stress, including 5 metallothionein-1 (MT1) isoform genes. In lung cells, addition of MT-1F in the medium attenuated PM2.5-induced H2O2 production while knockdown of MT1F gene expression increased H2O2 and IL-6 release induced by PM2.5. Our microarray experiments provided a global view of gene expression after in vitro PM2.5 exposure in human AM. The expression profile was most notable for differential expression of genes related to metal binding and oxidative stress, especially upregulation of MT1 isoform genes. Our findings suggest that metals associated with PM, e.g., zinc, copper, and arsenic, induce MT-1 and may be the primary mediators for PM-induced oxidative stress. Keywords: in vitro exposure, PM2.5 particle treatment, human alveolar macrophages
2008-05-01 | GSE10394 | GEO
Project description:Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.
2025-04-30 | GSE271469 | GEO
Project description:Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.
2025-04-30 | GSE272350 | GEO
Project description:Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.
2025-04-30 | GSE273470 | GEO
Project description:Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.
2025-08-01 | GSE273469 | GEO
Project description:Background: Diesel exhaust (DE) is the primary source of urban fine particulate matter, which has been associated with cardiovascular disease in epidemiological studies. These effects may be related to oxidative stress and systemic inflammation with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. Objectives: We conducted an exploratory study using microarray techniques to analyze whether global gene expression in peripheral blood mononuclear cells (PBMCs) can inform on potential mechanisms of effect of DE inhalation. Methods: In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in two-hour sessions. We isolated RNA (Trizol/Qiagen method) form PBMCs before, and two times after each exposure. RNA samples were arrayed using the Affymetrix® platform (GeneChip® Human Genome U133 Plus 2.0 Array). Results: Microarray analyses were conducted on five subjects with available RNA sample form exposures to FA and to the highest DE inhalation (200 µg/m³ of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets with significant evidence for differential expression (more than 1.5-fold up or down regulated with p < 0.05) were identified. These include genes involved in inflammatory response (e.g., IL8RA, TNFAIP6, FOS), oxidative stress (e.g., HMOX1, BAX, PRDX1,), and in biochemical pathways like mitogen-activated protein kinases (MAPK) and tight junction pathways. Conclusions: These data suggest that DE may exert time-dependent changes in gene expression in PBMCs in healthy individuals. Genes that may be affected by DE inhalation are involved in inflammatory and oxidative stress processes. Experiment Overall Design: We conducted a crossover, double-blind experiment, randomized to order of DE and filtered-air (FA) exposure with each participant exposed on four different days to each of four conditions: FA and DE calibrated to 50µg/m3 (DE50), 100µg/m3 (DE100), and 200µg/m3 (DE200) of fine particulate matter (PM2.5- particles with aerodynamic diameter 2.5µm or less). Exposure sessions were conducted at least 2 weeks apart.
2008-06-15 | E-GEOD-7462 | biostudies-arrayexpress
Project description:Disparate Oxidant-related Gene Expression of Human Small Airway Epithelium Compared to Autologous Alveolar Macrophages in Response to the In Vivo Oxidant Stress of Cigarette Smoking The oxidant burden of cigarette smoking induces lung cell dysfunction, and play a significant role in the pathogenesis of lung disease. Two cell populations directly exposed to the oxidants in cigarette smoke are the small airway epithelium and alveolar macrophages. Of these, the epithelium appears to be more vulnerable to smoking, becoming disordered in differentiation, repair and function, while alveolar macrophages become activated, without becoming diseased. In this context, we asked: for the same individuals, what is the baseline trancriptome of oxidant-related genes in small airway epithelium compared to alveolar macrophages and do the responses of the transcriptome of these 2 cell populations differ substantially to inhaled cigarette smoke? To address these questions we used microarray gene expression and TaqMan analysis to assess the gene expression profile of known oxidant-related genes in paired samples recovered by bronchoscopy from small airway epithelium and alveolar macrophages from the same healthy nonsmokers and normal smokers. Of the 155 oxidant-related genes surveyed, 122 (77%) were expressed in both cell populations in nonsmokers. However, of the genes expressed by both cell populations, oxidant related gene expression levels were higher in alveolar macrophages (67 genes, 43%) than small airway epithelium (37 genes, 24%). There were more oxidant-related genes uniquely expressed in the small airway epithelium (17%), than in alveolar macrophages (5%). In healthy smokers, the majority of oxidant-related genes were expressed in both cell populations, but there were marked differences in the numbers of oxidant-related genes that smoking up- or down-regulated. While smoking up-regulated 15 genes (10%) and down-regulated 7 genes (5%) in the small airway epithelium, smoking had far less effect on alveolar macrophages [only 4 (3%) genes up-regulated, and only 1 (0.6%) down-regulated]. Only a small number of smoking responsive oxidant-related genes overlapped between the two cell types (2 up-regulated, and no down-regulated genes). Consistent with this observation, pathway analysis of smoking-responsive genes in the small airway epithelium showed oxidant-related pathways dominated, but in alveolar macrophages immune-response pathways dominated. Thus, the responses of the oxidant-related transcriptome of cells with an identical genome and exposed to the same oxidant stress of cigarette smoking are very different, with responses of oxidant-related genes of alveolar macrophages far more subdued than that of small airway epithelium, consistent with the clinical observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to the oxidant stress of cigarette smoking. Gene expression profiles of known oxidant-related genes in paired samples recovered by bronchoscopy from small airway epithelium and alveolar macrophages from the same healthy nonsmokers and normal smokers.
2011-09-11 | E-GEOD-13931 | biostudies-arrayexpress
Project description:Rage null mice exposed to cigarette smoke demonstrate attenuated inflammatory, oxidative and ER stress responses in alveolar macrophages
| PRJNA304448 | ENA