title: Rosuvastatin reduces interleukin-6-induced expression of C-reactive protein in human hepatocytes in a STAT3- and C/EBP-dependent fashion.
abstract: OBJECTIVE
  It has been speculated that the reduction in vascular events by statins may not only be due to lowering of cholesterol, but also to the decrease in plasma C-reactive protein (CRP). In the present study we investigated the possibility that rosuvastatin directly affected CRP expression in stimulated human hepatocytes.
  
  
  METHODS
  Interleukin 6 (IL-6) stimulated human hepatoma cells (Hep3B) and primary human hepatocytes (PHH) were incubated with various concentrations of rosuvastatin (0.3 - 1 microM) for 24 hours. CRP expression was determined using ELISA and quantitative real-time RT-PCR. The activation of STAT3 and C/EBP was investigated utilizing transcription factor assays (TransAM).
  
  
  RESULTS
  IL-6 increased CRP secretion by up to 5-fold in Hep3B and 6.6-fold in PHH. Rosuvastatin reduced CRP expression by 32% and 46% in Hep3B and PHH, respectively. IL-6 increased CRP mRNA up to 32-fold. At 1 microM, rosuvastatin reduced CRP mRNA by 73% compared to IL-6-stimulated cells. IL-6 activated the transcription factors STAT3 and C/EBP up to 2.6-fold and 2.2-fold, respectively. Rosuvastatin (1 microM) attenuated the activation of STAT3 and C/EBP by 48% and 54%, respectively.
  
  
  CONCLUSIONS
  Our results show a direct inhibitory effect of rosuvastatin on IL-6-induced expression of CRP in liver cells. Statins may lower CRP by inhibiting its production in the liver rather than by exerting systemic anti-inflammatory effects. The effects of rosuvastatin in reducing the levels of CRP in plasma may have clinical utility in addition to its effects on atherogenic lipoproteins.
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Austria. claudia.mayer@klinikum-graz.at
authors.forename: C
authors.initials: C
authors.lastname: Mayer
authors.forename: H J
authors.initials: HJ
authors.lastname: Gruber
authors.forename: E M
authors.initials: EM
authors.lastname: Landl
authors.forename: S
authors.initials: S
authors.lastname: Pailer
authors.forename: H
authors.initials: H
authors.lastname: Scharnagl
authors.forename: M
authors.initials: M
authors.lastname: Truschnig-Wilders
authors.forename: W
authors.initials: W
authors.lastname: März
mesh_terms: D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000096:biosynthesis*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D005464:Fluorobenzenes / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007118:Immunoassay; D015850:Interleukin-6 / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000068718:Rosuvastatin Calcium; D050796:STAT3 Transcription Factor / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors
chemical_list: D000069059:Atorvastatin; D002097:C-Reactive Protein; D022762:CCAAT-Enhancer-Binding Proteins; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008798:Mevalonic Acid; D011743:Pyrimidines; D011758:Pyrroles; D012333:RNA, Messenger; D000068718:Rosuvastatin Calcium; D050796:STAT3 Transcription Factor; D013449:Sulfonamides; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors