IL-33 blockade impacts mediators of persistence and exacerbation in a model of chronic airway inflammation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA565175 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Summary: Blocking IL-33 signaling ameliorates inflammation, tissue remodeling and preserves lung function in a model of persistent and exacerbating airway disease. Background: Severe inflammatory airway diseases are associated with inflammation that fails to resolve, leading to structural changes and an overall environment primed for exacerbations. Objective: We sought to identify and inhibit pathways that perpetuate this heightened inflammatory state, as this could lead to therapies that allow for a more quiescent lung, less predisposed to symptoms and exacerbations. Methods: Using prolonged exposure to house dust mite (HDM) in mice, we developed a mouse model of persistent and exacerbating airway disease characterized by a mixed inflammatory phenotype. Results: We show that lung IL-33 drives inflammation and remodeling beyond the type 2 response classically associated with IL-33 signaling. IL-33 blockade with an IL-33 neutralizing antibody normalized established inflammation, and improved remodeling of both the lung epithelium and lung parenchyma. Specifically, IL-33 blockade normalized persisting and exacerbating inflammatory endpoints, including eosinophilic, neutrophilic and ST2+ CD4+ T cell infiltration. Importantly, we identified a key role for IL-33 in driving lung remodeling, as anti-IL-33 also reestablished the presence of ciliated cells over mucus producing cells and lowered myofibroblast numbers, even in the context of continuous allergen exposure, resulting in improved lung function. Conclusion: Overall, this study shows that elevated IL-33 drives a self-perpetuating amplification loop that retains the lung in a state of lasting inflammation and remodeled tissue, primed for exacerbations. Thus, IL-33 blockade may ameliorate symptoms and prevent exacerbations by quelling persistent inflammation and airway remodeling.
2019-09-13 | GSE137324 | GEO
Project description:To further unravel the potential molecular mechanisms involved in the loss of muscle function during an acute exacerbation, a cross-sectional microarray study was designed to compare the gene expression profile of the vastus lateralis muscle in patients with an acute COPD exacerbation and in stable COPD patients. Keywords: cross-sectional patient study A cross-sectional microarray study was designed. The microarray screening was performed on a vastus lateralis biopsy obtained from 4 patients with an acute COPD exacerbation and 5 stable COPD patients. No replicates or dye-swaps were included.
2009-03-13 | E-GEOD-10828 | biostudies-arrayexpress
Project description:Signaling via the arylhydrocarbon receptor (AhR) is thought to contribute to exacerbation of allergic asthma by anthropogenic pollution. The physiological role of AhR and its downstream targets CYP1 family members upon exposure to aeroallergens remain unknown. We seek to characterize the role of the AhR pathway for the regulation of allergic airway inflammation (AAI). We employed knockout animals of the AhR and its downstream target cytochrome P450 enzymes CYP1A1, CYP1A2 and CYP1B1 and subjected them to preclinical allergic asthma models (ragweed and house dust mite) to assess the role of AhR and CYP1 family members in allergic airway inflammation. Histological, transcriptional and functional assays were used to uncover relevant cell types and mechanistic insights. In the ragweed model, AhRKO/KO and CYP1B1KO/KO but not CYP1A2 KO/KO or CYP1A2KO/KO animals showed exacerbation of AAI including elevated infiltration of cells in the bronchoalveolar lavage fluid and increased serum levels of IgE and allergen-specific IgG1. AhR KO/KO and CYP1B1KO/KO animals showed also more severe reactions in HDM-induced allergic AAI. Bone marrow chimeras as well as qPCR analysis and immune fluorescence histology indicate that expression of CYP1B1 in non-hematopoietic cells – presumably lung epithelial cells – is necessary to prevent exacerbation of HDM-induced AAI. Mechanistically, we show that CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and thus potentially to deprivation from endogenous AhR ligands. Transcriptional analysis of primary lung epithelial cells indicates a functional link of the AhR to regulation of circadian clock genes at baseline and massive alteration of gene expression upon allergen exposure.
2022-05-23 | GSE158715 | GEO
Project description:A large, prospective, non-interventional study was designed to study gene expression changes in peripheral blood mononuclear cells (PBMCs) associated with asthma exacerbations over the course of a year. PBMC samples were collected from subjects at the time of the study visits defined as 1) Quiet: during stable disease at 3 month intervals, 2) Exacerbation: during a 14 day period of deteriorating asthma and 3) Follow-up: within 14 days after cessation of an exacerbation. Gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared. This series of samples comprises of peripheral blood mononuclear cells (PBMCs) collected during the following study visits (a) quiet (N=394 samples from 118 subjects), (b) exacerbation (N=166 samples from 118 subjects) and (c) follow-up (N=125 samples from 102 subjects)
2011-07-13 | E-GEOD-19301 | biostudies-arrayexpress
Project description:A Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis
2020-04-22 | PXD017818 | Pride
Project description:A large, prospective, non-interventional study was designed to study gene expression changes in peripheral blood mononuclear cells (PBMCs) associated with asthma exacerbations over the course of a year. PBMC samples were collected from subjects at the time of the study visits defined as 1) Quiet: during stable disease at 3 month intervals, 2) Exacerbation: during a 14 day period of deteriorating asthma and 3) Follow-up: within 14 days after cessation of an exacerbation. Gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared.
2011-07-14 | GSE19301 | GEO
Project description:To further unravel the potential molecular mechanisms involved in the loss of muscle function during an acute exacerbation, a cross-sectional microarray study was designed to compare the gene expression profile of the vastus lateralis muscle in patients with an acute COPD exacerbation and in stable COPD patients. Keywords: cross-sectional patient study
2009-03-14 | GSE10828 | GEO
Project description: Not available
| S-EPMC5694487 | biostudies-literature