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Related Experiment Video

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A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.

D H Perlmutter, C A Dinarello, P I Punsal

    The Journal of Clinical Investigation
    |November 1, 1986
    PubMed
    Summary

    Tumor necrosis factor (TNF) regulates liver gene expression, increasing acute-phase proteins like complement C3 and factor B. This indicates TNF

    Area of Science:

    • Immunology
    • Molecular Biology
    • Hepatology

    Background:

    • Tumor necrosis factor (TNF) is a monokine with effector functions similar to interleukin-1 (IL-1).
    • TNF shares characteristics with host responses to inflammation and tissue injury.

    Purpose of the Study:

    • To investigate whether recombinant human TNF regulates hepatic acute-phase gene expression.

    Main Methods:

    • Utilized human hepatoma cell lines (Hep G2, Hep 3B) and murine fibroblasts.
    • Administered picomolar concentrations of TNF to assess dose- and time-dependent effects.
    • Measured biosynthesis and gene expression of various complement proteins and acute-phase reactants.
    • Analyzed messenger RNA content to determine pre-translational regulation.

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    Main Results:

    • TNF significantly increased biosynthesis of complement proteins factor B and C3, and alpha 1 antichymotrypsin.
    • TNF decreased biosynthesis of albumin and transferrin.
    • TNF enhanced factor B gene expression but not C2 gene expression in transfected fibroblasts.
    • Observed pre-translational regulation of C3, factor B, and albumin expression by TNF.

    Conclusions:

    • Recombinant human TNF modulates hepatic acute-phase gene expression.
    • TNF's effects on acute-phase protein synthesis are mediated at the pre-translational level.