NHLBI TOPMed: Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid (CLIC)
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PROVIDER: PRJNA498559 | ENA |
REPOSITORIES: ENA
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Project description:NHLBI TOPMed: Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid (CLIC)
| PRJNA498558 | ENA
Project description:Inhaled corticosteroids (ICS) control airway inflammation in mild to moderate asthma by reducing inflammatory gene expression. However, incomplete understanding of the molecular mechanisms underpinning corticosteroid action hinders development of improved therapies for more severe disease. Microarray analysis was performed on RNA from biopsies taken from healthy individuals after receiving single dose of ICS to characterize corticosteroid-induced modulation of gene expression in the human airways.
2016-06-11 | GSE83233 | GEO
Project description:Inhaled corticosteroids (ICS) control airway inflammation in mild to moderate asthma by reducing inflammatory gene expression. However, incomplete understanding of the molecular mechanisms underpinning corticosteroid action hinders development of improved therapies for more severe disease. Microarray analysis was performed on RNA from biopsies taken from healthy individuals after receiving single dose of ICS to characterize corticosteroid-induced modulation of gene expression in the human airways. Healthy male, non-smoker, non-allergic volunteers (age 18-50 years) with normal lung function were recruited into a prospective, double-blind, placebo-controlled, randomized, two-period crossover study involving an initial screening visit, followed by two intervention visits. Participants were screened at visit 1 for fulfilment of the study eligibility criteria. At visit 2, volunteers were randomized to receive inhaled budesonide (1600 µg) or placebo, both via Turbuhaler. Two to three weeks later, at visit 3, participants received either budesonide or placebo, as appropriate to complete both study arms. Six hours after placebo or a budesonide inhalation, bronchial biopsies were obtained via bronchoscopy.
2016-06-11 | E-GEOD-83233 | biostudies-arrayexpress
Project description:Recent studies have highlighted the role of adrenal corticosteroid signaling in cardiac physiology and pathophysiology. It is known that glucocorticoids and aldosterone are able to bind glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and these ligand-receptor interactions are redundant. Therefore, it has been impossible to delineate how these nuclear receptors couple with corticosteroid ligands and differentially regulate gene expression for operation of their distinct functions in the heart. Here, to particularly define the role of GR, we applied ligand-based approach involving GR-specific agonist cortivazol (CVZ) and GR antagonist RU486, and performed microarray analysis using rat neonatal cardiomyocytes. We indicated that glucocorticoids appear to be a major determinant of GR-mediated gene expression when compared with aldosterone. Moreover, expression profiles of these genes highlighted numerous roles of glucocorticoids in various aspects of cardiac physiology. Experiment Overall Design: We analyzed gene expression changes after exposure of cells to corticosterone (COR), aldosterone (ALD), and cortivazol (CVZ) in the absence or presence of GR antagonist RU486. Since our preliminary experiments using several cell lines showed that expression of many GR target genes was induced by glucocorticoids in 3 h and to avoid secondary effects of the products of GR-regulated genes, we in the present study set the time periods of exposure to these ligands as 3 h. DNA microarray experiments were performed twice with the same protocol except for RU486 treatment.
2009-05-11 | E-GEOD-12752 | biostudies-arrayexpress
Project description:Recent studies have highlighted the role of adrenal corticosteroid signaling in cardiac physiology and pathophysiology. It is known that glucocorticoids and aldosterone are able to bind glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and these ligand-receptor interactions are redundant. Therefore, it has been impossible to delineate how these nuclear receptors couple with corticosteroid ligands and differentially regulate gene expression for operation of their distinct functions in the heart. Here, to particularly define the role of GR, we applied ligand-based approach involving GR-specific agonist cortivazol (CVZ) and GR antagonist RU486, and performed microarray analysis using rat neonatal cardiomyocytes. We indicated that glucocorticoids appear to be a major determinant of GR-mediated gene expression when compared with aldosterone. Moreover, expression profiles of these genes highlighted numerous roles of glucocorticoids in various aspects of cardiac physiology. Keywords: comparison of the effect of steroidal ligands
2009-05-01 | GSE12752 | GEO
Project description:Inhaled allergen challenge of subjects with allergic asthma allows the study of mechanisms involved in allergen-induced airway inflammation. The objective of this study was to identify changes in the plasma proteome associated with a late phase response (LPR) causing airway obstruction occurring 4-8 hours after the initial early response. Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed. Mass spectrometry data was analyzed using a linear regression to model the relationship between the degree of airway obstruction during the LPR and plasma proteome changes evoked by the inhaled allergen challenge. Inhaled allergen challenge induced changes in the plasma proteome including upregulation of the protease inhibitors alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Out of 396 quantified proteins, 150 showed a statistically significant change 23 hours post allergen challenge. Further proteomic changes were associated with the LPR, including altered levels of coagulation factors such as an increased factor XII A and a decreased von Willebrand factor. Allergic reactions to inhaled allergens in asthmatic subjects was associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors show the largest changes, likely to influence the inflammatory response. Of several other proteins altered in relation to the LPR, many are associated with coagulation.
2022-04-14 | PXD027091 | Pride
Project description:Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are understood, less is known about mechanisms controlling plasma corticosteroid transport. Here, we show hepatocyte KLF15 (Kruppel-like factor 15) controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of Serpina6, which encodes corticosteroid binding globulin (CBG). Klf15-deficient mice have profoundly low CBG, reduced plasma corticosteroid binding capacity, and heightened mortality during inflammatory stress. These defects are completely rescued by reconstituting CBG, supporting that KLF15 works primarily through CBG to control plasma corticosterone homeostasis. To understand transcriptional mechanisms, we generated the first KLF15 cistromes using newly engineered Klf153xFLAG mice. Unexpectedly, liver KLF15 is predominantly promoter-enriched, including Serpina6, where it binds a palindromic GC-rich motif, opens chromatin, and transactivates genes with minimal associated gene repression. Overall, we provide new mechanistic insight into KLF15 function and identify a hepatocyte-intrinsic transcriptional module that potently regulates systemic corticosteroid transport and inflammation.
2021-12-28 | GSE166083 | GEO
Project description:Although corticosteroids remain a mainstay of therapy for UC, a meta-regression of cohort studies in acute severe ulcerative colitis (UC) showed that 29% of patients fail corticosteroid therapy and require escalation of medical management or colectomy. We aimed to determine whether genes expressed in whole blood early following initiation of intravenous corticosteroid treatment can be associated with response. 20 corticosteroid responsive (PUCAI < 35 by day 5) and 20 corticosteroid resistant patients (PUCAI ≥ 35 by day 5 and need for 2nd line medical therapy or colectomy by hospital discharge) were selected from a prospectively accrued cohort of patients hospitalized for intravenous corticosteroid treatment of severe UC. Total RNA was extracted from blood samples collected on day 3 of intravenous corticosteroid therapy. The eluted transcriptomes were quantified on Affymetrix Human Gene 1.0 ST arrays. The data was analysed by the local-pooled error method for discovery of differential gene expression and false discovery rate correction was applied to adjust for multiple comparisons. P-values less than 0.05 after correction were considered significant.
2010-08-31 | E-GEOD-21231 | biostudies-arrayexpress
Project description:The aim of this project is to identify distinct temporal patterns of RNA expression in the skeletal muscle of rats following a bolus dose of the corticosteroid methylprednisolone. 51 RG_U34A chips were used over 17 time points. Keywords: other
2003-07-16 | GSE490 | GEO