RNA-seq analysis of human asthma bronchoalveolar lavage (BAL) cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136587 | GEO | 2021/04/01
REPOSITORIES: GEO
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Project description:RNA-seq analysis of human asthma bronchoalveolar lavage (BAL) cells
| PRJNA562768 | ENA
Project description:Background: A subset of asthmatics does not respond to steroid therapy and therefore is at risk for escalation of disease severity. The cause of corticosteroid resistant (CR) asthma is unknown. Gene microarray technologies have the potential to substantiate new hypotheses regarding the etiology of corticosteroid resistance. Methods: Gene microarray analysis was performed with bronchoalveolar lavage (BAL) cells of CR and corticosteroid sensitive (CS) asthmatics. Increased gene expression was verified with real time PCR and at the protein level by ELISA. Findings: Microarray analyses demonstrated significantly higher levels (over two-fold increase, p<0.05) of TNF-alpha, IL-1alpha, IL-1beta, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, CCL20 gene expression in BAL cells of CR than CS asthmatics. These findings, confirmed by RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively-activated macrophages, Arginase I and CCL24, were decreased in CR asthmatics. Genes associated with activation of the LPS signaling pathway (EGR1, DUSP2, MAIL, TNFAIP3) were significantly elevated in CR BAL samples (p<0.05). CR asthmatics had significantly higher amounts (1444.0±457.3 pg per mg of total protein) of LPS in BAL fluid than CS asthmatics (270.5±216.0 pg; p<0.05). Prolonged exposure to LPS induced functional steroid resistance to dexamethasone (DEX) in normal monocytes, demonstrated by persistently elevated IL-6 levels in the presence of DEX. Interpretation: Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from CR asthmatics suggest that LPS exposure may contribute to CR asthma. Experiment Overall Design: Patients with a diagnosis of asthma according to American Thoracic Society criteria were selected for evaluation. Asthmatics had a baseline FEV1% predicted of 55% to 85% of predicted, a beta2-adrenergic response of â¥12% of baseline FEV1% predicted and/or a methacholine PC20 value of â¤8 mg/ml. Asthma patients were further subdivided in CR and CS groups, based on their response to steroids. The definition was based on change in FEV1 % predicted over a one-week course of 40 mg/day of oral prednisone. Asthmatic patients were defined as CS if they had an increase in FEV1% predicted of greater than 15% after a one-week course of prednisone, and as CR if less than 12% change in FEV1% predicted was observed. None of the asthmatic subjects recruited for this study had evidence for other types of lung diseases. None of the subjects had received systemic corticosteroid therapy for at least one month prior to bronchoscopy. All subjects provided written informed consent to participate in the study. The study was approved by the Institutional Review Board at National Jewish Medical and Research Center, Denver, CO. Gene array studies of BAL macrophages were performed in 3 CR and 3 CS asthmatics.
2009-07-01 | E-GEOD-7368 | biostudies-arrayexpress
Project description:Clinical bronchoalveolar lavage (BAL) samples Targeted loci
| PRJNA408304 | ENA
Project description:We performed high-throughput single-cell RNA sequence using mouse BAL cells to identify subpopulations of airway cells.
2023-01-21 | GSE166290 | GEO
Project description:Segmental allergen challenge increases the percentage of eosinophils in bronchoalveolar lavage (BAL) cells. Mepolizumab, an anti-IL-5 therapeutic antibody, decreases the number of eosinophils in bronchoalveolar lavages (BAL). The use of both procedures allows to define genes that are either expressed by eosinophils or dependent on eosinophil presence in the airways.
2013-05-01 | GSE46159 | GEO
Project description:Segmental allergen challenge increases the percentage of eosinophils in bronchoalveolar lavage (BAL) cells. Mepolizumab, an anti-IL-5 therapeutic antibody, decreases the number of eosinophils in bronchoalveolar lavages (BAL). The use of both procedures allows to define genes that are either expressed by eosinophils or dependent on eosinophil presence in the airways. Cells from Bronchoalveolar lavages (BAL) are obtained by bronchoscopy before (V5) and 48 h after a segmental allergen challenge (V6) in atopic and mild astmatics. This procedure was repeated in the same two subjects 2 months later and 1 month after an injection of mepolizumab (V22 is before challenge and V23 after challenge). Cells were immediately lysed and isolated total RNAs were analyzed using the Human Genome 1.0 ST GeneChip arrays (Affymetrix, Santa Clara, CA).
2013-05-01 | E-GEOD-46159 | biostudies-arrayexpress
Project description:Ozone, the major component of air pollution, is an oxidant gas. Inhalation of high ambient levels of ozone causes oxidative stress and airway inflammation. To assess the biological responses of airway inflammatory cells to ozone-induced oxidative stress, we examined the gene expression of airway inflammatory cells in response to inhalation of ozone. Nineteen subjects, with and without asthma, were exposed to clean air (0 ppb), low (100ppb), and high (200ppb) ambient levels of ozone for 4 hours on three separate occasions in a climate-controlled chamber followed by bronchoscopy with bronchoalveolar lavage (BAL) 20 hours after the end of exposure in a repeated measure design. The BAL cells mRNA expression was examined using Affymetrix GeneChip Microarray.
2015-06-15 | E-GEOD-58682 | biostudies-arrayexpress
Project description:The aim of the project was to explore large extracellular vesicles capacity to seperate non lung cancer from lung cancer cases. A case control study of patients suspected for lung cancer (12 non lung cancer and 12 lung cancers). The raw files are labeled according to clinical status. Small and large extracellular vesicles were isolated by differential centrifugation. The proteome of full BAL, vesicle depleted BAL, small and large extracellular vesicles were characterized by LC-MS. Small extracellular vesicles were further analyzed by nanoparticle tracking analysis, Transmission electron microscopy and western blots.
2020-12-15 | PXD021988 | Pride
Project description:All-trans retinoic acid (ATRA) is a potent retinoid, which has been used successfully in different clinical settings as a potential drug to treat COPD and emphysema. In alveolar macrophages, ATRA selectively down-regulates MMP-9 and up-regulates TIMP-1 expression. In the present study, we analyzed additional genes modulated by ATRA by performing mRNA expression array on alveolar macrophages after treatment with ATRA. Total RNA was isolated from BAL cells cultivated either in the presence of liposomal ATRA or left untreated for 3 days. Total RNA from five independent donors were pooled at 0.4 µg each to give a final amount of 2µg. This pooled RNA was used for microarray analysis using the Affymatrix array
2010-09-04 | E-GEOD-23704 | biostudies-arrayexpress
Project description:Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy can be used as a model to safely induce transient airway inflammation in the human lung. The LPS challenge model enables investigation of cellular mechanisms involved in pulmonary inflammatory processes as well as pharmacodynamic analysis of investigational drugs for the treatment of respiratory diseases. Aim of this work was to describe the transcriptomic profile of the human segmental LPS challenge model with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage fluid (BAL) and biopsies were sampled from twenty-eight smoking, healthy subjects, followed by segmental LPS challenge and saline control challenge. Twenty-four hours post instillation, BAL and biopsies were collected from the challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced for subsequent data analysis. Differential gene expression analysis resulted in 6316 upregulated differentially expressed genes (DEGs) and 241 downregulated DEG in BAL, but only one downregulated DEG in biopsy samples after LPS challenge compared to saline challenge. Upregulated DEG in BAL were related to molecular functions such as “Inflammatory response” or “antimicrobial humoral immune response mediated by antimicrobial peptide”, enriched biological processes such as “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt signaling pathway”, “Ras signaling pathway” or “JAK-STAT signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia (CAP). Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.
2024-03-01 | E-MTAB-13318 | biostudies-arrayexpress