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Nijmegen, Netherlands

Toonen E.J.M.,MSD Research Laboratories | Fleuren W.W.M.,Radboud University Nijmegen | Fleuren W.W.M.,Netherlands Bioinformatics Center 5 | Nassander U.,MSD Research Laboratories | And 5 more authors.
Pharmacogenomics | Year: 2011

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. © 2011 Future Medicine Ltd. Source

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