Prednisolone-induced changes in gene-expression profiles in healthy volunteers

Erik J M Toonen, Wilco W M Fleuren, Ulla Nässander, Marie-José C van Lierop, Susanne Bauerschmidt, Wim H A Dokter, Wynand Alkema

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)985-998
JournalPharmacogenomics
Volume12
Issue number7
DOIs
Publication statusPublished - 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

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  • Cite this

    Toonen, E. J. M., Fleuren, W. W. M., Nässander, U., van Lierop, M-J. C., Bauerschmidt, S., Dokter, W. H. A., & Alkema, W. (2011). Prednisolone-induced changes in gene-expression profiles in healthy volunteers. Pharmacogenomics, 12(7), 985-998. https://doi.org/10.2217/pgs.11.34