Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mayer, C; Gruber, HJ; Landl, EM; Pailer, S; Scharnagl, H; Truschnig-Wilders, M; März, W.
Rosuvastatin reduces interleukin-6-induced expression of C-reactive protein in human hepatocytes in a STAT3- and C/EBP-dependent fashion.
INT J CLIN PHARM THERAPEUTICS. 2007; 45(6): 319-327.
Doi: 10.5414/CPP45319
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- Führende Autor*innen der Med Uni Graz
- Bernecker Claudia
- Co-Autor*innen der Med Uni Graz
- Gruber Hans-Jürgen
- März Winfried
- Matzhold Eva-Maria
- Pailer Sabine
- Scharnagl Hubert
- Truschnig-Wilders Martini
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- C-Reactive Protein - biosynthesis
- CCAAT-Enhancer-Binding Proteins - physiology
- Cells, Cultured - physiology
- Fluorobenzenes - pharmacology
- Hepatocytes - drug effects
- Heptanoic Acids - pharmacology
- Humans - pharmacology
- Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
- Immunoassay - pharmacology
- Interleukin-6 - antagonists and inhibitors
- Mevalonic Acid - pharmacology
- Pyrimidines - pharmacology
- Pyrroles - pharmacology
- RNA, Messenger - biosynthesis
- STAT3 Transcription Factor - physiology
- Sulfonamides - pharmacology
- Transcription Factors - pharmacology
- Find related publications in this database (Keywords)
- C-reactive protein
- interleukin-6
- inflammation
- atherogenesis
- rosuvastatin