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Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists.

Abstract
C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.
AuthorsSongwen Zhang, Qiangyuan Liu, Juan Wang, Douglas C Harnish
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 379 Issue 2 Pg. 476-9 (Feb 06 2009) ISSN: 1090-2104 [Electronic] United States
PMID19118524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • Interleukin-6
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • farnesoid X-activated receptor
  • C-Reactive Protein
Topics
  • Acute-Phase Reaction (genetics, immunology)
  • Animals
  • C-Reactive Protein (antagonists & inhibitors, biosynthesis)
  • Cell Line, Tumor
  • DNA-Binding Proteins (agonists, genetics, physiology)
  • Gene Expression (drug effects)
  • Humans
  • Interleukin-6 (pharmacology, physiology)
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering (genetics)
  • Receptors, Cytoplasmic and Nuclear (agonists, genetics, physiology)
  • Transcription Factors (agonists, genetics, physiology)

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