title: Prednisolone-induced changes in gene-expression profiles in healthy volunteers.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MSD Research Laboratories, Oss, The Netherlands.
authors.forename: Erik J M
authors.initials: EJ
authors.lastname: Toonen
authors.forename: Wilco W M
authors.initials: WW
authors.lastname: Fleuren
authors.forename: Ulla
authors.initials: U
authors.lastname: Nässander
authors.forename: Marie-José C
authors.initials: MJ
authors.lastname: van Lierop
authors.forename: Susanne
authors.initials: S
authors.lastname: Bauerschmidt
authors.forename: Wim H A
authors.initials: WH
authors.lastname: Dokter
authors.forename: Wynand
authors.initials: W
authors.lastname: Alkema
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D011239:Prednisolone; D006854:Hydrocortisone