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Transcriptome landscape of human primary monocytes response upon different ligand glucocorticoids

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE115514 | GEO | 2019/03/03

REPOSITORIES: GEO

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Transcriptomes of human monocytes and monocyte-derived macrophages with or without glucocorticoid treatment

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

The epigenome and glucocorticoid receptor binding of human monocytes and monocyte-derived macrophages with or without glucocorticoid treatment

2019-03-03 | GSE109438 | GEO

The chromatin architecture at glucocorticoid-induced genes PER1 and IRAK3

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Transcriptome landscape of HeLa response upon triamcinolone acetonide

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

Comparison of cellular and transcriptional responses to 1,25-dihydroxyvitamin D3 and glucocorticoids in peripheral blood mononuclear cells

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

Comparison of cellular and transcriptional responses to 1,25-dihydroxyvitamin D3 and glucocorticoids in peripheral blood mononuclear cells

2013-08-21 | GSE50012 | GEO

Yakimchuk2019 - Mathematical modeling of immune modulation by glucocorticoids

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

Differential effect of glucocorticoids on the activation of monocytes and macrophages

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

Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response

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

Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD1 expression on NK cells

Project description:Purpose: Controlling the balance between immunity and immunopathology is crucial for host resistance to pathogens. Upon infection, activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to the production of glucocorticoids (GCs). However, the pleiotropic effects of these steroid hormones make it difficult to decipher their precise role in vivo. Our purpose was to study how GCs regulate the function of group 1 ILCs in spleen and liver upon Murine Cytomegalovirus (MCMV) infection. Methods: We studied the in vivo effect of endogenous GCs released upon MCMV infection on NK cells in spleen and liver and ILC1s in the liver. We compared WT mice with GRNcr1-iCre mice, in which the gene encoding for GC receptor (GR) is selectively deleted in Ncr1+ cells. Results: We found that the regulation of NK function by the GR is required for host protection against MCMV. Mechanistically, endogenous GCs produced shortly after infection induce the selective and tissue-specific expression of the immune checkpoint PD1 on NK cells. This GC-PD1 pathway mediates its immunoregulatory functions by limiting interferon (IFN)-g production by splenic NK cells, preventing lethal immunopathology. Importantly, this regulation does not compromise viral clearance. Conclusions:The fine-tuning of a selective subset of ILCs by the HPA axis preserves tissue integrity without impairing pathogen elimination, revealing a novel aspect of neuro-immune regulation.

2018-05-24 | GSE114827 | GEO

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