Mus musculus
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ABSTRACT:
PROVIDER: PRJNA89979 | ENA |
REPOSITORIES: ENA
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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:Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD. Keywords: IL13, mucus, goblet cell RNA was isolated from primary culture airway epithelial cells grown at air-liquid interface, treated with or without IL-13 for 21 days.
2012-12-04 | E-GEOD-37693 | biostudies-arrayexpress
Project description:Gene Expression Effects of IL-13 on Primary Human Airway Epithelial Cells
| PRJNA162689 | ENA
Project description:Human airway epithelia (HAE) undergo inflammation-induced remodeling in chronic lung diseases such as asthma and chronic bronchitis. The role of type 2 inflammation-induced epithelial remodeling in SARS-CoV-2 infection and the course of COVID-19 is unclear, moreover, there is discrepancy in the literature regarding the potential benefit of treatments that modulate type 2 inflammation. We investigated the role of IL-13-induced inflammation on SARS-CoV-2 binding/entry, replication, and host response in primary HAE cells in vitro and in a model of mouse-adapted SARS-CoV-2 in vivo. IL-13 protected airway epithelial cells from SARS-CoV-2 infection in vitro by decreasing the abundance of ACE2- expressing ciliated cells rather than by neutralization in the airway surface liquid or by interferon-mediated antiviral effects. In contrast, IL-13 worsened the severity of disease in mice in vivo; the effects were mediated by eicosanoid signaling and were abolished in mice deficient in the phospholipase A2 enzyme PLA2G2D. We conclude that IL-13-induced inflammation affects multiple steps of SARS-CoV-2-induced disease pathogenesis. Whereas IL-13-induced inflammation may be protective against initial infection at the airway epithelium, it enhances disease severity once infection progresses in vivo; blockade of IL-13 and/or eicosanoid signaling may be protective against progression to severe lung disease.
2024-06-26 | GSE249304 | GEO
Project description:BACKGROUND: The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To investigate this poorly understood pathobiology, we characterized IL-13 effects on human airway epithelial cultures using single cell RNA-sequencing, finding that IL-13 generated a novel transcriptional state for each cell type. Specifically, we discovered a mucus secretory program induced by IL-13 in all cell types which converted both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. The IL-13-remodeled epithelium secreted a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrested mucociliary motion. Signatures of IL-13-induced cellular remodeling were mirrored by transcriptional signatures characteristic of the nasal airway epithelium within T2H versus T2-low asthmatic children. Our results reveal the epithelium-wide scope of T2H asthma and present novel therapeutic targets for restoring normal epithelial function.
2020-07-13 | GSE145013 | 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:Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD. Keywords: IL13, mucus, goblet cell
2012-12-04 | GSE37693 | 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:By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that ITLN1 gene expression is significantly reduced and ITLN-1 protein expression is lost through a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies one of the first biomarkers and targetable pathways for the treatment of mucus obstruction in asthma.
2024-04-04 | GSE254127 | GEO