title: Comparison of cellular and transcriptional responses to 1,25-dihydroxyvitamin d3 and glucocorticoids in peripheral blood mononuclear cells.
abstract: 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.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Kupfer
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Maranville
authors.forename: Shaneen S
authors.initials: SS
authors.lastname: Baxter
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Anna
authors.initials: A
authors.lastname: Di Rienzo
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000328:Adult; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004579:Electron Transport / Q000235:genetics; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D014815:Vitamins / Q000494:pharmacology; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D014815:Vitamins; D003907:Dexamethasone; D002117:Calcitriol