Prednisolone-induced changes in gene-expression profiles in healthy volunteers
| Autor: | Wilco W. M. Fleuren, Susanne Bauerschmidt, Ulla Nässander, Marie-Jose van Lierop, Wim H. A. Dokter, Wynand Alkema, Erik J M Toonen |
|---|---|
| Přispěvatelé: | Data Sciences for Life Science & Health |
| Rok vydání: | 2011 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Chemical and physical biology [NCMLS 7] Hydrocortisone cd4-positive t-lymphocytes/drug effects Prednisolone CD14 Anti-Inflammatory Agents Lipopolysaccharide Receptors immunosuppressive agents/administration & dosage insulin-secreting cells/drug effects lipopolysaccharide receptors/analysis Pharmacology Biology monocytes/drug effects Monocytes Biological pathway Young Adult In vivo Insulin-Secreting Cells Gene expression adults gene expression profiling Genetics medicine humans Adverse effect metabolisme Health aging / healthy living Pathogenesis and modulation of inflammation [IGMD 5] Middle Aged hydrocortisone/blood Gene signature Gene expression profiling cd4 lymphocyte count Immunology Molecular Medicine prednisolone/administration & dosage anti-inflammatory agents/administration & dosage Immunosuppressive Agents medicine.drug |
| Zdroj: | Pharmacogenomics, 12, 985-98 Pharmacogenomics, 12, 7, pp. 985-98 Pharmacogenomics, 12(7), 985-998. Ashley |
| ISSN: | 1462-2416 |
| Popis: | 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 submitted 5 January 2011; Revision submitted 24 February 2011 |
| Databáze: | OpenAIRE |
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