Linking VEGF Deficiency and IL-33 Upregulation in Chronic Obstructive Pulmonary Disease.
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ABSTRACT:
SUBMITTER: Byers DE
PROVIDER: S-EPMC6827072 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
2003-07-16 | GSE475 | GEO
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a respiratory disorder with increasing prevalence and mortality. It is associated with airway obstruction, increased airway hyper-responsiveness (AHR), and ongoing airway and lung inflammation dominated by CD8 lymphocytes and neutrophils. Single-nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene have been associated with AHR and COPD.ObjectiveTo assess whether SNPs in ADAM33 are associated with the severity of AHR and airway inflammation in COPD.MethodsEight SNPs in ADAM33 (F+1, Q-1, S_1, S_2, ST+5, T_1, T_2, V_4) were genotyped in 111 patients with COPD (96 males, 69 current smokers, mean (standard deviation (SD)), aged 62 (8) years, median pack-years 42 (IQR 31-55), mean postbronchodilator forced expiratory volume in 1 s (FEV(1))% predicted 63 (9). Provocative concentration of methacholine causing a decrease in FEV(1) of 20% (PC(20) methacholine), sputum and bronchial biopsies were collected.ResultsPatients with the ST+5 AA genotype had more severe AHR, higher numbers of sputum inflammatory cells and CD8 cells in bronchial biopsies than patients with the GG genotype (p = 0.03, 0.05 and 0.01, respectively). CD8 cell numbers were lower in patients carrying the minor allele of SNP T_1 and T_2, and homozygotic minor variants of SNP S_2 compared with the wild type (p = 0.02, 0.01 and 0.02, respectively).ConclusionsThis is the first study revealing that SNPs in a gene that confers susceptibility to COPD in the general population-that is, ADAM33-are associated with AHR and airway inflammation in COPD. These findings constitute an important step forward in linking gene polymorphisms with COPD pathophysiology, thereby possibly contributing to better treatments for this progressive and disabling disease in the future.
| S-EPMC2117167 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) and lung cancer are linked diseases, with both the incidence of and risk of death from non-small cell lung cancer being increased by the presence of COPD. Despite numerous well-performed epidemiological studies having described this link over the past 30 years, the operative mechanisms remain elusive. One of the major obstacles to advancement in the field has been the lack of patient cohorts that have been phenotyped for both COPD and lung cancer. This review discusses several studies performed over the past few years highlighting the impact of COPD on the outcomes of patients with non-small cell lung cancer with respect to lung cancer screening, immune-based therapies, and lung cancer chemoprevention.
| S-EPMC6322005 | biostudies-literature
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
2014-08-14 | E-GEOD-60399 | biostudies-arrayexpress
Project description:The aim of the present study was to investigate the roles of type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) in chronic obstructive pulmonary disease (COPD). Serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and COPD patients. ILC2 cells from the peripheral blood of COPD patients were stimulated with IL-33 or neutralizing ST2 antibody+IL-33 in vitro. The cell viability was assessed using a Cell Counting Kit-8 assay. ELISA was used to detect serum IL-33 and the levels of IL-4, IL-5, IL-6, IL-13 and soluble ST2 (sST2) in the culture supernatant. The percentage of ILC2 cells was measured by flow cytometry. The mRNA expression levels of GATA binding protein 3 (GATA3), RAR-related orphan receptor (ROR)α, ST2 and prostaglandin D2 receptor 2 (CRTH2) were detected by reverse transcription-quantitative PCR. It was revealed that IL-33, IL-5, IL-6 and IL-13 were significantly elevated in peripheral blood of patients with COPD. The proportion of ILC2s in peripheral blood of COPD patients was significantly increased, and the expression of RORA and CRTH2 was increased. The proportion of ST2+ ILC2 cells was significantly increased. After 48 h of IL-33 stimulation in vitro, the ratio of linage-CD45+CD127+CRTH2+ cells reached a maximum. In addition, the viability of ILC2 cells, the expression levels of RORA, GATA3, ST2 and CRTH2 mRNA and the cytokines IL-4, IL-6, IL-5, IL-13 and sST2 were significantly increased. These effects were abrogated by treatment with anti-ST2. In conclusion, IL-33 is upregulated in the serum of patients with COPD and the proportion of ILC2s among the PBMCs is increased. IL-33 may promote the proliferation of ILC2 cells and secrete type 2 T-helper cell cytokines to participate in the immune response in COPD.
| S-EPMC6755436 | biostudies-literature
Project description: Not available
| S-EPMC8106745 | biostudies-literature
Project description:Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13-dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production.
| S-EPMC3754239 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) Metagenome
| PRJNA647843 | ENA
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients.
2014-08-14 | GSE60399 | GEO
Project description:BackgroundLung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models.MethodsMUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3? were measured by ELISA. The effect of MUC1 on inflammation and corticosteroid anti-inflammatory effects was measured using cell siRNA in vitro and Muc1-KO in vivo animal models.ResultsMUC1-CT expression was downregulated in lung tissue, bronchial epithelial cells and lung neutrophils from smokers (n?=?11) and COPD (n?=?11) patients compared with healthy subjects (n?=?10). MUC1 was correlated with FEV1% (??=?0.7479; p?<?0.0001) in smokers and COPD patients. Cigarette smoke extract (CSE) decreased the expression of MUC1 and induced corticosteroid resistance in human primary bronchial epithelial cells and human neutrophils. MUC1 Gene silencing using siRNA-MUC1 impaired the anti-inflammatory effects of dexamethasone and reduced glucocorticoid response element activation. Dexamethasone promoted glucocorticoid receptor alpha (GR?) and MUC1-CT nuclear translocation and co-localization that was inhibited by CSE. Lung function decline and inflammation induced by lipopolysaccharide and cigarette smoke in Muc1 KO mice was resistant to dexamethasone.ConclusionsThese results confirm a role for MUC1-CT mediating corticosteroid efficacy in COPD.
| S-EPMC6247701 | biostudies-literature