Transcriptome landscape of human primary monocytes response upon different ligand glucocorticoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE115514 | GEO | 2019/03/03
REPOSITORIES: GEO
Similar Datasets
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases due to their potent immune suppressive properties.
2019-03-03 | GSE109439 | GEO
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases due to their potent immune suppressive properties.
2019-03-03 | GSE109438 | GEO
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties.
2019-03-03 | GSE117057 | GEO
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties.
2019-03-03 | GSE115669 | GEO
Project description:Glucocorticoids (GC) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are steroid hormones with anti-inflammatory properties with enhanced effects when combined. We previously showed that transcriptional response to GCs was correlated with inter-individual and inter-ethnic cellular response. Here, we profiled cellular and transcriptional responses to 1,25(OH)2 D3 from the same donors. We studied cellular response to combined treatment with GCs and 1,25(OH)2 D3 in a subset of individuals least responsive to GCs. We found that combination treatment had significantly greater inhibition of proliferation than with either steroid hormone alone. Overlapping differentially expressed (DE) genes between the two hormones were enriched for adaptive and innate immune processes. Non-overlapping differentially expressed genes with 1,25(OH)2 D3 treatment were enriched for pathways involving the electron transport chain, while with GC treatment, non-overlapping genes were enriched for RNA-related processes. These results suggest that 1,25(OH)2 D3 enhances GC anti-inflammatory properties through a number of shared and non-shared transcriptionally-mediated pathways. Total RNA was obtained from aliquots of peripheral blood mononuclear cells treated with 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) for 8 and 24 hours. These data were analyzed together with previously published data from expression analysis of PBMC aliquots collected in parallel to these and treated with dexamethasone or vehicle (EtOH).
2013-08-21 | E-GEOD-50012 | biostudies-arrayexpress
Project description:Glucocorticoids (GC) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are steroid hormones with anti-inflammatory properties with enhanced effects when combined. We previously showed that transcriptional response to GCs was correlated with inter-individual and inter-ethnic cellular response. Here, we profiled cellular and transcriptional responses to 1,25(OH)2 D3 from the same donors. We studied cellular response to combined treatment with GCs and 1,25(OH)2 D3 in a subset of individuals least responsive to GCs. We found that combination treatment had significantly greater inhibition of proliferation than with either steroid hormone alone. Overlapping differentially expressed (DE) genes between the two hormones were enriched for adaptive and innate immune processes. Non-overlapping differentially expressed genes with 1,25(OH)2 D3 treatment were enriched for pathways involving the electron transport chain, while with GC treatment, non-overlapping genes were enriched for RNA-related processes. These results suggest that 1,25(OH)2 D3 enhances GC anti-inflammatory properties through a number of shared and non-shared transcriptionally-mediated pathways.
2013-08-21 | GSE50012 | GEO
Project description:Mathematical modeling of immune modulation by glucocorticoids
Konstantin Yakimchuk
https://doi.org/10.1016/j.biosystems.2019.104066
Abstract
The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.
2020-01-06 | MODEL1912170005 | BioModels
Project description:The Glucocorticoid receptor (GR/NR3C1) is expressed in almost all immune cells. Glucocorticoids (GCs) are potent regulators of inflammation with effects mainly immunosuppressive. While, GCs have pleiotropic effects on Macrophages exhibiting complex properties with enhancing as well as suppressive effects on inflammatory processes depending on their stage of differentiation and activation, the mechanisms of GCs actions on Monocytes and Macrophages and their contribution to systemic anti-inflammatory effects remain unclear. Previously we have demonstrated that NLRP3 expression is induced by GCs in macrophages differentiated from monocytes-THP-1 but not in monocytes. These findings raise the possibility that the stage of myeloid differentiation and the cellular environment dictates the actions of GR from a pro- or anti-inflammatory perspective. Moreover, our preliminary results using the same cell line THP-1 show that the differentiation process from monocytes to macrophages also is related with the downregulation of GR induced by dex.
2020-01-27 | GSE135130 | GEO
Project description:Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in AfricanAmericans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects. Total RNA was obtained from paired aliquots of peripheral blood mononuclear cells treated with dexamethasone or vehicle (EtOH) for 8 and 24 hours.
2012-02-01 | E-GEOD-33649 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) reduce the expression of many genes induced in inflammatory conditions in vivo or by pro-inflammatory stimuli in vitro acting on the Glucocorticoid receptor (GR/NR3C1). However, GCs have pleiotropic effects on the immune system. Monocytes and macrophages are important cells of the innate immune system, exhibiting complex properties with enhancing as well as suppressive effects on inflammatory processes depending on their stage of activation and differentiation. Macrophages contribute to host defense, tissue remodeling and wound healing The mechanisms of GCs actions on monocytes and macrophages and their contribution to systemic anti-inflammatory effects remain unclear. These effects on activation GCs in monocytes and macrophages were investigated using the human monocytic cell line THP-1 and differentiation protocol PMA. Monocytes-THP1 and macrophages derived-monocytes were exposed for 6 hours to 100 nM of dexamethasone (Dex) and analyzed by microarrays. In macrophages-derived monocytes with respect to monocytes-THP-1, the number of genes differentially regulated was almost twice, among these, genes related with pro-inflammatory pathways, like TNFa, CXCL1 and GZMA. Interestingly, one of the genes differentially regulated (decreased) in macrophages exposed to Dex was the GR itself. If this effect modifies the inflammatory function of macrophages derived-monocyte is a question that will be evaluated through this study.
2020-01-27 | GSE135165 | GEO