E-GEOD-3183
Ontology highlight
ABSTRACT:
PROVIDER: E-GEOD-3183 | ExpressionAtlas | 2025-01-24
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-3183-analysis-methods.tsv | Tabular | |||
| E-GEOD-3183-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-3183-configuration.xml | Xml | |||
| E-GEOD-3183-percentile-ranks.tsv | Tabular | |||
| E-GEOD-3183.condensed-sdrf.tsv | Tabular |
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Project description:We performed RNA sequencing of gene expression of differentiated primary human bronchial epithelial cells derived from control and asthmatic patients, stimulated with IL-13. The Type 2 Asthma mediator IL-13 was described to induce airway hyperresponsiveness, goblet cell metaplasia, mucus hypersecretion and airway remoddeling including impairment of epithelial barrier integrity. We investigated differential expression of SARS-CoV-2 related host gene expression as well as genes involved in N-linked glycosylation upon IL-13 in bronchial epithelial cells. Top IL-13 affected pathways included ion- and transmembrane transport, lipid metabolic processed and protein glycosylation.
2023-01-30 | GSE206510 | GEO
Project description:Selective stimulation of IL-4 receptor on smooth muscle induces airway hyper-responsiveness in mice. Abstract: Production of the cytokines IL-4 and IL-13 is increased in both human asthma and mouse asthma models and Stat6 activation by the common IL-4/IL-13R drives most mouse model pathophysiology, including airway hyperresponsiveness (AHR). However, the precise cellular mechanisms through which IL-4Rα induces AHR remain unclear. Overzealous bronchial smooth muscle constriction is thought to underlie AHR in human asthma, but the smooth muscle contribution to AHR has never been directly assessed. Furthermore, differences in mouse vs. human airway anatomy and observations that selective IL-13 stimulation of Stat6 in airway epithelium induces murine AHR raise questions about the importance of direct IL-4R effects on smooth muscle in murine asthma models and relevance of these models to human asthma. Using transgenic mice in which smooth muscle is the only cell type that expresses or fails to express IL-4Rα, we demonstrate that direct smooth muscle activation by IL-4, IL-13, or allergen is sufficient, but not necessary, to induce AHR and show that 5 genes known to promote smooth muscle migration, proliferation and contractility are activated by IL-13 in smooth muscle in vivo. These observations demonstrate that IL-4Rα promotes AHR through multiple mechanisms and provide a model for testing smooth muscle-directed asthma therapeutics.
2011-01-07 | GSE26476 | GEO
Project description:Selective stimulation of IL-4 receptor on smooth muscle induces airway hyper-responsiveness in mice. Abstract: Production of the cytokines IL-4 and IL-13 is increased in both human asthma and mouse asthma models and Stat6 activation by the common IL-4/IL-13R drives most mouse model pathophysiology, including airway hyperresponsiveness (AHR). However, the precise cellular mechanisms through which IL-4Rα induces AHR remain unclear. Overzealous bronchial smooth muscle constriction is thought to underlie AHR in human asthma, but the smooth muscle contribution to AHR has never been directly assessed. Furthermore, differences in mouse vs. human airway anatomy and observations that selective IL-13 stimulation of Stat6 in airway epithelium induces murine AHR raise questions about the importance of direct IL-4R effects on smooth muscle in murine asthma models and relevance of these models to human asthma. Using transgenic mice in which smooth muscle is the only cell type that expresses or fails to express IL-4Rα, we demonstrate that direct smooth muscle activation by IL-4, IL-13, or allergen is sufficient, but not necessary, to induce AHR and show that 5 genes known to promote smooth muscle migration, proliferation and contractility are activated by IL-13 in smooth muscle in vivo. These observations demonstrate that IL-4Rα promotes AHR through multiple mechanisms and provide a model for testing smooth muscle-directed asthma therapeutics. For the microarray aspect of of the study, there were three groups of mice: 1. IL4R gene knockout (KO) mice 2. WT mice 3. IL4R KO mice that were also transgenic for a gene construct that expressed IL4R under the control of the smooth muscle-specific promoter from the SMP8 gene All mice were subjected to intratracheal IL13 exposure for 7 days, and whole lung RNA was prepared for microarray analysis 24 hours after the last instillation. Per treatment and genotype: Two RNA pools were made from four mice each. These were labeled and hybridized to make a total of 6 microarrays. RNA was labeled with the standard Affymetrix 3' labeling protocol to make cDNA that was hybridized to Mouse MOE 430 plus 2.0 GeneChips. Gene transcripts were identified that differed in their relative expression as a function of IL4R expression on the smooth muscle cells.
2011-01-07 | E-GEOD-26476 | biostudies-arrayexpress
Project description:The IL-13 is a central mediator of allergic asthma. This project investigates the mechanisms by which IL-13 elicits the symptoms of asthma.
2007-09-29 | E-GEOD-1301 | biostudies-arrayexpress
Project description:The IL-13 is a central mediator of allergic asthma. This project investigates the mechanisms by which IL-13 elicits the symptoms of asthma. Keywords: other
2004-04-14 | GSE1301 | GEO
Project description:Bronchial asthma is associated with type 2 immune responses induced by components of adaptive as well as innate immunity. Although innate cytokines such as IL-25 have been shown to play key roles in development of airway hyperreactivity (AHR), little is known of innate molecules that regulate IL-25-mediated airway inflammation. We found that blockade of repulsive guidance molecule b (RGMb) in an experimental murine model of asthma blocked the development of AHR, a cardinal feature of asthma, and that RGMb is expressed on F4/80+CD11b+CD11cneg macrophages (RGMb+ macrophages), which accumulated in the lungs of OVA-sensitized and challenged mice, but not in naïve mice. Moreover, we found that a large fraction of the RGMb+ macrophages expressed the IL-25 receptor IL-17RB and produced IL-13. IL-25 was critical for the development of AHR in our model, since mice deficient in IL-17RB did not develop AHR. Finally, treatment with anti-RGMb mAb during the challenge phase of the protocol after allergen sensitization effectively prevented the development of AHR and airway inflammation, suggesting for the first time that RGMb+ cells, including RGMb+ macrophages, play critical roles in allergen-induced asthma. We used microarrays to compare the gene expression patterns in WT mice sensitized and challenged with OVA that were treated with either RGMb mAb or an isotype control.
2016-03-14 | GSE79156 | GEO
Project description:Bronchial asthma is associated with type 2 immune responses induced by components of adaptive as well as innate immunity. Although innate cytokines such as IL-25 have been shown to play key roles in development of airway hyperreactivity (AHR), little is known of innate molecules that regulate IL-25-mediated airway inflammation. We found that blockade of repulsive guidance molecule b (RGMb) in an experimental murine model of asthma blocked the development of AHR, a cardinal feature of asthma, and that RGMb is expressed on F4/80+CD11b+CD11cneg macrophages (RGMb+ macrophages), which accumulated in the lungs of OVA-sensitized and challenged mice, but not in naïve mice. Moreover, we found that a large fraction of the RGMb+ macrophages expressed the IL-25 receptor IL-17RB and produced IL-13. IL-25 was critical for the development of AHR in our model, since mice deficient in IL-17RB did not develop AHR. Finally, treatment with anti-RGMb mAb during the challenge phase of the protocol after allergen sensitization effectively prevented the development of AHR and airway inflammation, suggesting for the first time that RGMb+ cells, including RGMb+ macrophages, play critical roles in allergen-induced asthma. We used microarrays to compare the gene expression patterns in WT mice sensitized and challenged with OVA that were treated with either RGMb mAb or an isotype control. First replicate: 3 control samples (mice sensitized and challenged with saline), 3 RGMb mAb samples, 3 isotype samples; 2nd replicate: 3 control samples, 3 RGMb mAb samples, 2 isotype samples. Lung tissues were harvested at the same treatment time point in all groups.
2016-03-14 | E-GEOD-79156 | biostudies-arrayexpress
Project description:Background: Dupilumab, a fully human monoclonal antibody that binds IL-4Ra and inhibits signaling of both IL-4 and IL-13, has shown efficacy across multiple diseases with underlying type 2 signatures and is approved for treatment of asthma, atopic dermatitis and chronic sinusitis with nasal polyposis. We sought to provide a comprehensive analysis of the redundant and distinct roles of IL-4 and IL-13 in type 2 inflammation and report dupilumab mechanisms of action. Methods: Using primary cell assays and a mouse model of house dust mite induced asthma, we compared IL-4 versus IL-13 versus IL-4Ra blockers. Results: Intranasal administration of either IL-4 or IL-13 confers an asthma-like phenotype in mice by inducing immune cell lung infiltration, including eosinophils, increasing cytokine/chemokine expression and mucus production, thus demonstrating redundant functions of these cytokines. We further teased out their respective contributions using human in vitro culture systems. Then, in a mouse asthma model by comparing in head to head studies, either IL-4 or IL-13 inhibition to dual IL-4/IL-13 inhibition, we demonstrate that blockade of both IL-4 and IL-13 is required to broadly block type 2 inflammation, which translates to protection from allergen-induced lung function impairment. Notably, only dual IL-4/IL-13 blockade prevented eosinophil infiltration into lung tissue without affecting circulating eosinophils, demonstrating that tissue, but not circulating eosinophils contribute to disease pathology. Conclusions: Overall, these data support IL-4 and IL-13 as key drivers of type 2 inflammation, and help provide insight into the therapeutic mechanism of dupilumab, a dual IL-4/IL-13 blocker, in multiple type 2 diseases.
2019-11-25 | GSE140900 | GEO
Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4Rα that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials
2014-12-04 | GSE59294 | GEO
Project description:Multi-walled carbon nanotubes (MWCNT) cause lung fibrosis in rodents and exacerbate airway fibrosis in the mouse ovalbumin model of allergic asthma. Interleukin 13 (IL-13) is a key cytokine secreted by T helper type 2 (Th2) cells. IL-13 is up-regulated in human asthma and animal models that activate pro-fibrotic and pro-proliferative cell signaling cascades in human lung fibroblasts (HLF). This study tested the hypothesis that IL-13 alters the gene expression profile of HLF exposed to MWCNT. Carbon black nanoparticles (CBNP) were also compared to MWCNT as they are relatively inert nanoparticles that do not cause fibrosis. Confluent, quiescent cultures of HLF were treated with 10 ng/ml IL-13 or serum-free defined medium (vehicle) for 24 hours prior to treatment with 10 M-BM-5g/cm2 MWCNT or CBNP. At 4, 24, or 48 hours following nanoparticle exposure, total RNA was isolated and gene expression was measured using the Affymetrix Human Genome U133A2.0 Array. The data were analyzed using the JMP Genomics statistical platform. IL-13 and MWCNT each caused changes in the expression of distinct gene subsets over the time-course investigated. The combination of IL-13 and MWCNT resulted in a gene expression profile that was distinct from patterns induced or suppressed by either IL-13 or MWCNT alone. CBNP caused changes in gene expression that were distinct from IL-13 or MWCNT. Interestingly, the combination of IL-13 and MWCNT increased the expression of IL-17A and increased collagen (Col1A1), while MWCNT alone increased interferon-inducible protein-27 (IFI27), suggesting that Th2 microenvironment containing IL-13 shifts MWCNT-induced gene expression from a Th1 to a Th17 gene expression profile. These data provide insight into the mechanisms by which MWCNT alter the biology of fibroblasts during normal and allergic inflammatory conditions. Adult Lung Fibroblasts were treated with 10 M-BM-5g/cm2 MWCNT, CBNP, or vehicle with or without IL-13 for 4 hours, 24 hours, or 48 hours.
2013-05-29 | E-GEOD-43515 | biostudies-arrayexpress