Functional classes of bronchial mucosa genes that are differentially expressed in asthma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15823 | GEO | 2009/04/24
SECONDARY ACCESSION(S): PRJNA116743
REPOSITORIES: GEO
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Project description:Asthma is a complex syndrome associated with episodic decompensations provoked by aeroaller-gen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bron-choalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial aller-gen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and cor-relation with airway inflammation. SBP-Ag induced statistically significant changes in 549 fea-tures that mapped to 72 uniquely identified metabolites. From these features, two distinct induci-ble metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that in-formed the presence of asthma-relevant pathways, including unsaturated fatty acid produc-tion/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen chal-lenge induces distinct metabolic responses in humans, providing insight into pathogenic and pro-tective endotypes in allergic asthma.
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Project description:Transcriptional profiling of lung bronchial biospsy mRNA from asthmatics Two-condition experiment, mRNA from asthma bronchial biopsies for test channel and Stratagene Universal Human Reference RNA for reference channel.
2015-09-08 | E-GEOD-69497 | biostudies-arrayexpress
Project description:The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. We used micro array to profile gene expression of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. 17 subjects were included in a cross-sectional study (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). RNA was extracted from isolated and cultured epithelial cells from bronchial brushes and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array).
2013-02-05 | E-GEOD-44037 | biostudies-arrayexpress
Project description:Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.
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Project description:Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by the airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that the upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and that this is modulated by the presence of asthma and allergic rhinitis. Identification of dsRNA-induced gene expression profiles by microarray of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. 17 subjects were included in a cross-sectional study (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). RNA was extracted from isolated and cultured epithelial cells that were stimulated with Poly(I:C) for 24 hours from bronchial brushes and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array).
2013-10-18 | E-GEOD-51392 | biostudies-arrayexpress
Project description:Allergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers. 4 healthy controls without history of allergy and asthma and 4 allergic asthmatic subjects according to the American Thoracic Society (ATS) criteria were selected
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Project description:Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.
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Project description:Biological mechanisms explaining asthma control improvement following bronchial thermoplasty are still not well understood. We used a large-scale transcriptomic approach to evaluate the transcriptome of bronchial epithelial cell (BEC) obtained before and after bronchial thermoplasty treatment (BT).
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Project description:Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A2s (PLA2s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro-asthmatic lipid mediators, but an understanding of the association between individual PLA2 subtypes and asthma is still incomplete. Here, we show that group III secreted PLA2 (sPLA2-III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA2-III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)-induced asthma model, Pla2g3 knockout (-/-) mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA-specific IgE production, and type 2 cytokine expression as compared to Pla2g3 wild-type (+/+) mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA-challenged Pla2g3-/- mice relative to Pla2g3+/+ mice. LPA receptor 2 agonists suppressed thymic stromal lymphopoietin expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in Pla2g3-/- mice, suggesting that sPLA2-III negatively regulates allergen-induced asthma at least by producing LPA. Thus, the activation of the sPLA2-III-LPA pathway may be a new therapeutic target for allergic asthma. Microarray gene profiling of the bronchial epithelial cells isolated from OVA-challenged lung revealed the increased expression of various chemokines and type 2 epithelial cytokines in bronchial epithelial cells from Pla2g3-/- mice as compared to those from Pla2g3+/+ mice following OVA challenge.
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