Abstract
BACKGROUND: Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive drugs. However, prolonged use at a medium or high dose is hampered by side effects of which the metabolic side effects are most evident. Relatively little is known about their effect on gene-expression in vivo, the effect on cell subpopulations and the relation to the efficacy and side effects of GCs.
AIM: To identify and compare prednisolone-induced gene signatures in CD4⁺ T lymphocytes and CD14⁺ monocytes derived from healthy volunteers and to link these signatures to underlying biological pathways involved in metabolic adverse effects.
MATERIALS & METHODS: Whole-genome expression profiling was performed on CD4⁺ T lymphocytes and CD14⁺ monocytes derived from healthy volunteers treated with prednisolone. Text-mining analyses was used to link genes to pathways involved in metabolic adverse events.
RESULTS: Induction of gene-expression was much stronger in CD4⁺ T lymphocytes than in CD14⁺ monocytes with respect to fold changes, but the number of truly cell-specific genes where a strong prednisolone effect in one cell type was accompanied by a total lack of prednisolone effect in the other cell type, was relatively low. Subsequently, a large set of genes was identified with a strong link to metabolic processes, for some of which the association with GCs is novel.
CONCLUSION: The identified gene signatures provide new starting points for further study into GC-induced transcriptional regulation in vivo and the mechanisms underlying GC-mediated metabolic side effects.
Original language | English |
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Pages (from-to) | 985-998 |
Journal | Pharmacogenomics |
Volume | 12 |
Issue number | 7 |
DOIs | |
Publication status | Published - 25 Jul 2011 |
Keywords
- adults
- anti-inflammatory agents/administration & dosage
- cd4 lymphocyte count
- cd4-positive t-lymphocytes/drug effects
- gene expression profiling
- humans
- hydrocortisone/blood
- immunosuppressive agents/administration & dosage
- insulin-secreting cells/drug effects
- lipopolysaccharide receptors/analysis
- monocytes/drug effects
- prednisolone/administration & dosage