title: Identification of gene signatures for prednisolone-induced metabolic dysfunction in collagen-induced arthritic mice.
abstract: BACKGROUND
  Prednisolone is a potent anti-inflammatory glucocorticoid (GC) but chronic use is hampered by metabolic side effects. Little is known about the long-term effects of GCs on gene-expression in vivo during inflammation.
  
  
  OBJECTIVE
  Identify gene signatures underlying prednisolone-induced metabolic side effects in a complex in vivo inflammatory setting after long-term treatment.
  
  
  METHODS
  We performed whole-genome expression profiling in liver and muscle from arthritic and nonarthritic mice treated with several doses of prednisolone for 3 weeks and used text-mining to link gene signatures to metabolic pathways.
  
  
  RESULTS
  Prednisolone-induced gene signatures were highly tissue specific. We identified a short-list of genes significantly affected by both prednisolone and inflammation in liver and involved in glucose and fatty acid metabolism. For several of these genes the association with GCs is novel.
  
  
  CONCLUSIONS
  The identified gene signatures may provide useful starting points for the development of GCs with a better safety profile.
authors.affiliation: Division Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ellero-Simatos
authors.forename: Wilco W M
authors.initials: WW
authors.lastname: Fleuren
authors.forename: Susanne
authors.initials: S
authors.lastname: Bauerschmidt
authors.forename: Wim H A
authors.initials: WH
authors.lastname: Dokter
authors.forename: Erik J M
authors.initials: EJ
authors.lastname: Toonen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001168:Arthritis / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D003095:Collagen Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D011239:Prednisolone; D005947:Glucose