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 µM) 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 µM, 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 µM) 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.

Author Details

Authors

• C. Mayer
• H.-J. Gruber
• E.-M. Landl
• S. Pailer
• H. Scharnagl
• M. Truschnig- Wilders
• W. März

Departments

• ¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics,
  Medical University Graz, Austria,
• ² LURIC study LLC, Freiburg, Germany

Address

C. Mayer
Clinical Institute of Medical and Chemical Laboratory Diagnostics
Medical University Graz
Auenbruggerplatz 15
8036 Graz, Austria
Email: [email protected]

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