Gene Expression Effects of IL-13 on Primary Human Airway Epithelial Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE37693 | GEO | 2012/12/04
SECONDARY ACCESSION(S): PRJNA162689
REPOSITORIES: GEO
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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.
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Project description:IL13 exposure results in a distinct gene expression profile in human airway epithelia. We investigated whether this expression profile can be used to identify compounds able to block goblet cell metaplasia We used microarrays to determine transcriptional changes in cultures of primary human airway epithelia grown at the air-liquid interface after exposure to 20 ng/mL recombinant human IL13
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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.
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Project description:Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the United States and is caused primarily by cigarette smoking. Increased numbers of mucus-producing secretory (“goblet”) cells defined as goblet cell metaplasia or hyperplasia (GCMH), contributes significantly to COPD pathophysiology. The objective of this study was to determine whether NOTCH signaling regulates goblet cell differentiation in response to cigarette smoke. To this end, primary human bronchial epithelial cells (HBECs) from nonsmokers and COPD smokers were differentiated in vitro on air-liquid interface and exposed to cigarette smoke extract (CSE) for 7 days. NOTCH signaling activity was modulated using (1) the NOTCH/γ-secretase inhibitor Dibenzazepine (DBZ), (2) lentiviral over-expression of the NOTCH3-intracellular domain (NICD3) or (3) NOTCH3-specific siRNA. Cell differentiation and response to CSE were evaluated by qPCR, Western blotting, immunostaining and RNA-Seq. Our data demonstrate that CSE exposure of nonsmoker airway epithelium induced goblet cell differentiation characteristic of GCMH. Treatment with DBZ suppressed CSE-dependent induction of goblet cell differentiation. Furthermore, CSE induced NOTCH3 activation, as revealed by increased NOTCH3 nuclear localization and elevated NICD3 protein levels. Over-expression of NICD3 increased expression of the goblet cell associated genes SPDEF and MUC5AC, whereas NOTCH3 knockdown suppressed CSE-mediated induction of SPDEF and MUC5AC. Finally, CSE exposure of COPD airway epithelium induced goblet cell differentiation in a NOTCH3-dependent manner. These results identify NOTCH3 activation as one of the important mechanisms by which cigarette smoke induces goblet cell differentiation, thus providing a potential strategy to control GCMH-related pathologies in smokers and patients with COPD.
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Project description:Epigenetic changes have been implicated in pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and remodeling, induced miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. For our studies, we used a well-characterized transgenic mouse model of allergic airway inflammation induced by IL13. In this model, IL13 is conditionally overexpressed in the mouse lung when treated with doxycycline. Upon IL13 induction, these mice showed inflammatory cell infiltration, pronounced emphysema, increased pulmonary compliance, lung volume enlargement, mucus metaplasia, and increased expression of matrix metalloproteinases and cathepsins in the lung. The CC10-rtTA-IL13 transgenic (TG) and wildtype (WT) mice were treated with doxycycline for seven days. Mice were euthanized and the left upper lobes from all mice were removed for RNA extraction using the TRIzol method.
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Project description:Epigenetic changes have been implicated in pathogenesis of asthma. We sought to determine if IL13, a key cytokine in airway inflammation and remodeling, induced miRNAs expression changes in the airways in conjunction with its transcriptional gene regulation. For our studies, we used a well-characterized transgenic mouse model of allergic airway inflammation induced by IL13. In this model, IL13 is conditionally overexpressed in the mouse lung when treated with doxycycline. Upon IL13 induction, these mice showed inflammatory cell infiltration, pronounced emphysema, increased pulmonary compliance, lung volume enlargement, mucus metaplasia, and increased expression of matrix metalloproteinases and cathepsins in the lung.
2012-02-23 | GSE35980 | GEO
Project description:Asthma is a common chronic inflammatory airway condition with a strong genetic and inheritability component, as siblings and first-degree relatives of those with the disease are often affected. For our studies, we used a well-characterized transgenic mouse model of allergic airway inflammation induced by IL13. In this model, IL13 is conditionally overexpressed in the mouse lung when treated with doxycycline. Upon IL13 induction, these mice showed inflammatory cell infiltration, pronounced emphysema, increased pulmonary compliance, lung volume enlargement, mucus metaplasia, and increased expression of matrix metalloproteinases and cathepsins in the lung. We performed gene expression microarray to examine the changes in gene expression during IL13-induced allergic airway inflammation. The CC10-rtTA-IL13 transgenic (TG) and wildtype (WT) mice were treated with doxycycline for seven days. Mice were euthanized and the left upper lobes from all mice were removed for RNA extraction using the TRIzol method.
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