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Related Experiment Videos

Endotoxin-stimulated macrophages decrease bile acid uptake in WIF-B cells, a rat hepatoma hybrid cell line.

E Sturm1, T L Zimmerman, A R Crawford

  • 1Program in Gastrointestinal Pathology, Yale Liver Center and Yale University Medical School, New Haven, CT, USA.

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

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Stimulated macrophages release cytokines that decrease bile salt uptake by liver cells after endotoxin exposure. This macrophage-mediated cytokine release is crucial for the endotoxin-induced cholestatic effect.

Area of Science:

  • Hepatology
  • Immunology
  • Cell Biology

Background:

  • Endotoxemia causes changes in liver function, specifically affecting the hepatocellular sodium-taurocholate-cotransporting polypeptide (NTCP).
  • Macrophages play a role in immune responses and can influence liver cell function through secreted factors.

Purpose of the Study:

  • To investigate the role of stimulated macrophages in mediating the endotoxin-induced down-regulation of hepatocellular bile salt uptake.
  • To determine if cytokines secreted by macrophages are responsible for reduced NTCP function.

Main Methods:

  • In vitro exposure of mouse macrophages (IC-21) to lipopolysaccharide (LPS).
  • Incubation of WIF-B rat hepatoma cells with LPS-conditioned medium (CM) or recombinant cytokines (TNF-alpha, IL-1beta, IL-6).

Related Experiment Videos

  • Measurement of [(3)H]taurocholate uptake and NTCP mRNA expression in WIF-B cells and primary hepatocytes.

    • Main Results:

    • LPS-stimulated macrophages secreted significantly increased levels of TNF-alpha, IL-1beta, and IL-6.
    • Exposure to CM or recombinant cytokines significantly reduced [(3)H]taurocholate uptake in WIF-B cells.
    • NTCP mRNA expression was reduced in WIF-B cells and primary hepatocytes exposed to CM or TNF-alpha.
    • Blocking antibodies against TNF-alpha, IL-1beta, and IL-6 partially restored bile salt uptake.

    Conclusions:

    • Macrophages are essential transducers in the endotoxin-induced down-regulation of hepatocellular bile salt uptake.
    • Cytokines TNF-alpha, IL-1beta, and IL-6 secreted by activated macrophages mediate the cholestatic effect of reduced bile salt uptake.
    • This study highlights a key mechanism in endotoxemia-induced liver dysfunction.