Similarity of Gene Expression Patterns in Human Alveolar Macrophages in Response to P. aeruginosa and B. cepacia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12245 | GEO | 2008/07/26
SECONDARY ACCESSION(S): PRJNA113711
REPOSITORIES: GEO
Similar Datasets
Project description:To determine if differences in the severity of pulmonary infection in cystic fibrosis been seen in late isolates od Pseudomonas aeruginosa and Burkholderia cepacia are associated with differences in the initial repsonse of alveolar macrophages (AM) to these pathogens, we assessed gene expression changes in human AM in response to infection with a laboratoty strain, early and late clinical isolates of P. aeruginosa, and B. cepacia. Experiment Overall Design: Alveolar macrophages were obtained from bronchoalveolar lavage. Experiment Overall Design: Two clinical strains isolated from the sputum of an individual with CF, AD2A and AD15B (provided by J. Burns, University of Washington, Seattle). AD2A is an early clinical isolate, and AD15B is a late clinical isolate; both were derived from the same individual.
2008-10-21 | E-GEOD-12245 | biostudies-arrayexpress
Project description:Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%. 4 never smokers and 4 active smokers were recruited for the study. After bronchoalveolar lavage and RNA isolation, gene expression was measured using Affymetrix Human Exon 1.0 ST arrays.
2012-10-02 | E-GEOD-34517 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Existing experimental data in our lab showed significantly different levels of virulence of "early" and "late" P. aeruginosa infection isolates in a C. elegans slow killing model. We wished to examine the expression profile of these isolates in order to explore genes that may be responsible for the observed differences. The expression profiles of two pairs of isolates (four isolates in total) were compared to each other using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating virulence in these isolates. Data analysis was carried out using BIOCONDUCTOR software. Keywords: Comparative strain hybridization
2011-12-31 | GSE33275 | GEO
Project description:Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%.
2012-10-02 | GSE34517 | GEO
Project description:Cigarette smoking is the leading cause of the respiratory diseases collectively known as chronic obstructive pulmonary disease (COPD). While the pathogenesis of COPD is complex, there is abundant evidence that alveolar macrophages (AM) play an important role. Based on the concept that COPD is a slow-progressing disorder likely involving multiple mediators released by AM activated by cigarette smoke, the present study focuses on the identification of previously unrecognized genes that may be linked to early events in the molecular pathogenesis of COPD, as opposed to factors associated with the presence of disease. To accomplish this, microarray analysis using Affymetrix microarrays was used to carry out an unbiased survey of the differences in gene expression profiles in the AM of phenotypically normal, ~20 pack-yr smokers compared to healthy non-smokers. Although smoking did not alter the global gene expression pattern of AM, 75 genes were modulated by smoking, with 40 genes up-regulated and 35 down-regulated in the AM of smokers compared to non-smokers. Most of these genes belong to the functional categories of immune/inflammatory response, cell adhesion and extracellular matrix, proteolysis and antiproteolysis, lysosomal function, antioxidant-related, signal transduction and regulation of transcription. Of these 75 genes, 69 have not been previously recognized to be up- or down-regulated in alveolar macrophages in association with smoking or COPD, including genes coding for proteins belonging to all of the above categories, and others belonging to various functional categories or of unknown function. These observations suggest that gene expression responses of alveolar macrophages associated with the stress of cigarette smoking are more complex than previously thought, and offer a variety of new insights into the complex pathogenesis of smoking-induced lung diseases. Experiment Overall Design: 5 non smokers and 5 smokers Experiment Overall Design: Alveolar macrophages were obtained from bronchoalveolar lavage
2007-09-06 | E-GEOD-3212 | biostudies-arrayexpress
Project description:Tolerance is a major defense strategy against infection. During the host response to pathogens, tolerance restricts inflammatory damage to tissues, maintaining the long-term integrity of organs. The mechanisms that establish tolerance are poorly understood. We analyzed pulmonary isolates of Pseudomonas aeruginosa that evolved to coexist with tolerant hosts and found that these opportunistic pathogens facilitate tolerance by stimulating ketogenesis. Ketone body production in the airway limits the accumulation of detrimental factors that injure the lung, such as inflammatory cytokines and effector phagocytes. Although ketones are typically synthesized in the liver, in situ metabolo-transcriptomic studies revealed that P. aeruginosa drives their generation in the lung by co-opting the metabolism of alveolar macrophages, which are pulmonary cells of hepatic origin. This phenomenon was restricted to clinical isolates and not observed with laboratory strains of P. aeruginosa , confirming the unique metabolo-tolerogenic properties of ESKAPE pathogens adapted to the human lung.
2023-10-12 | GSE203352 | GEO
Project description:Cigarette smoking is the leading cause of emphysema in the United States. Alveolar macrophages play a critical role in the inflammation-mediated remodeling of the lung parenchyma in emphysema. However, the exact gene pathways and the role of DNA methylation in moderating this pathological transformation are not known. In order to more exactly understand this process, we compared genome-wide expression and methylation signatures of alveolar macrophages isolated from heavy smokers with those isolated from non-smoking controls. We found enrichment of differential methylation in genes from immune system and inflammatory pathways as determined by standard pathway analysis. Consistent with recent findings, significant methylation changes were particularly enriched in the areas flanking CpG islands (CpG shores). Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune system and inflammatory pathways. We conclude that alveolar macrophages from the lungs of smokers demonstrate coordinated changes in DNA methylation and gene expression that link to inflammation pathways. We suggest that further studies of DNA methylation in immune and inflammation-related gene expression are needed to understand the pathogenesis of emphysema and other smoking-related diseases. Expression analysis of 13 smokers vs. 10 non-smokers on the Affymetrix Exon Array. This submission represents the expression component of the study.
2011-02-03 | E-GEOD-27002 | 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:Pseudomonas aeruginosa (P. aeruginosa) lung infection is a significant cause of mortality in patients with cystic fibrosis (CF). Existing experimental data in our lab showed significantly different levels of virulence of "early" and "late" P. aeruginosa infection isolates in a C. elegans slow killing model. We wished to examine the expression profile of these isolates in order to explore genes that may be responsible for the observed differences. The expression profiles of two pairs of isolates (four isolates in total) were compared to each other using the Affymetrix P. aeruginosa PAO1 genome array, to gain insight into properties mediating virulence in these isolates. Data analysis was carried out using BIOCONDUCTOR software. Keywords: Comparative strain hybridization Two pairs of isolates (four isolates in total) were compared to each other when grown on Nematode Growth Medium (NGM).
2011-12-31 | E-GEOD-33275 | biostudies-arrayexpress
Project description:Matrix metalloproteinase-9 (MMP-9) expression is up-regulated in alveolar macrophages (AM) of HIV1+ smokers who develop emphysema. Based on the knowledge that lung epithelial lining fluid (ELF) of HIV1+ smokers has increased levels of inflammatory cytokines compared to HIV1- smokers, we hypothesized up-regulation of lung cytokines in HIV1+ smokers may be functionally related to increased MMP-9 expression. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1‾ healthy nonsmokers, HIV1‾ healthy smokers, HIV1‾ smokers with low diffusing capacity (DLCO) , HIV1 + nonsmokers, and HIV1 + smokers with low DLCO. Among several pro-inflammatory cytokines elevated in ELF associated with smoking and HIV1+, increased levels of the Th17-related cytokine IL-23 were found in HIV1- smokers with low DLCO and HIV1+ smokers and nonsmokers. Relative IL-23 gene expression was significantly increased in AM of HIV1+ individuals, with greater expression in AM of HIV1+ smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. Since AM purified by adherence contain a small number of lymphocytes, we hy-pothesized that in an AM/lymphocyte co-culture system, IL-23 would up-regulate MMP-9. IL-23 stimulation of AM/lymphocyte co-cultures in vitro induced increased MMP-9 mRNA levels and protein. AM of healthy individuals did not express IL-23 receptors (IL-23R), lung T lymphocytes express IL-23R and interact with AM in order to up-regulate MMP-9. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+ smokers and suggests that Th-17 related inflammation may play a role. IL-23 upregulates MMP-9 expression in human alveolar macrophages via a T lymphocyte/alveolar macrophage interaction, suggesting a possible role for Th-17 related inflammation in accelerated emphysema in HIV1+ smokers.
2024-06-05 | GSE64598 | GEO