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

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 suppressive properties.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109438 | GEO | 2019/03/03

REPOSITORIES: GEO

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

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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).

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