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Related Experiment Videos

Bile acids modulate the interferon signalling pathway.

P Podevin1, O Rosmorduc, F Conti

  • 1INSERM U402, Paris, France.

Hepatology (Baltimore, Md.)
|May 29, 1999
PubMed
Summary
This summary is machine-generated.

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Bile acids, common in liver disease, were found to inhibit the interferon (IFN) pathway, reducing antiviral protein production. This may explain why some patients with chronic viral liver diseases do not respond to IFN therapy.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Cholestasis and bile acids are known to inhibit 2', 5' oligoadenylate synthetase (OAS) activity in liver cells.
  • The impact of bile acids on the broader interferon (IFN) pathway activation in liver cells remained unclear.

Purpose of the Study:

  • To investigate the influence of bile acids on interferon (IFN) pathway activation in hepatoma cell lines.
  • To determine the mechanism by which bile acids affect IFN-induced antiviral protein expression.
  • To assess the relevance of these findings at physiological bile acid concentrations.

Main Methods:

  • Hepatoma cell lines (HepG2) and engineered CHO cells expressing human NTCP were treated with bile acids.
  • IFN-induced 2',5' OAS activity, MxA and OAS p100 protein expression (Western blot), STATs tyrosine phosphorylation, and MxA promoter activity were measured.

Related Experiment Videos

  • The role of protein kinase C (PKC) and the Na+-dependent taurocholate cotransporting polypeptide (NTCP) transporter were investigated.
  • Main Results:

    • Bile acids inhibited IFN-induced 2',5' OAS activity and the expression of antiviral proteins MxA and OAS p100 in HepG2 cells.
    • Chenodeoxycholic acid (CDCA) reduced MxA promoter activity by 60% but did not affect STATs tyrosine phosphorylation.
    • Inhibition of the IFN pathway by bile acids was observed at physiological concentrations (12-50 micromol/L) in NTCP-expressing cells.

    Conclusions:

    • Bile acids significantly inhibit the induction of key proteins involved in the antiviral activity of interferon.
    • This inhibitory effect, particularly at physiological concentrations, may contribute to the reduced responsiveness to interferon therapy observed in patients with advanced chronic viral liver diseases.
    • Further research into bile acid modulation of the IFN pathway could lead to improved therapeutic strategies for viral liver diseases.