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

Onderzoeksoutput: ArticleAcademicpeer review

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)985-998
TijdschriftPharmacogenomics
Volume12
Nummer van het tijdschrift7
DOI's
StatusPublished - 25 jul 2011

Keywords

  • metabolisme

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