Bicyclol attenuates pro-inflammatory cytokine and chemokine productions in CpG-DNA-stimulated L02 hepatocytes by inhibiting p65-NF-kappaB and p38-MAPK activation

Pharmazie. 2010 Mar;65(3):206-12.

Abstract

Bicyclol, a novel synthetic anti-hepatitis drug, has a potent hepatocyte-protective effect and a mild anti-hepatitis virus function. However, its pharmaceutical effects and mechanism are still unclear. In the present study, we found that bicyclol pre-treatment could attenuate the production of the inflammatory cytokines (TNF-alpha and IL-18) and chemokines (MCP-1, MIP-1 alpha and Rantes) and inhibit the activation of the p65-NF-kappaB and MAPK signaling pathways in CpG-ODN 2006-stimulated L02 hepatocytes in a dose-dependent manner. Collectively, these results suggest that bicyclol could exert its hepatocyte-protective effect through attenuating CpG-ODN 2006-stimulated inflammatory responses in L02 hepatocytes, which might be associated with the activations of NF-kappaB and MAPK pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / pharmacology*
  • Blotting, Western
  • Chemokines / biosynthesis*
  • CpG Islands
  • Cytokines / biosynthesis*
  • DNA / pharmacology*
  • DNA, Viral / pharmacology
  • Enzyme Activation / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / isolation & purification
  • Signal Transduction / drug effects
  • Stimulation, Chemical
  • Toll-Like Receptor 9 / physiology
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / metabolism*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Biphenyl Compounds
  • Chemokines
  • Cytokines
  • DNA, Viral
  • Nuclear Proteins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Transcription Factor RelA
  • DNA
  • bicyclol
  • p38 Mitogen-Activated Protein Kinases