Rapid modulation of tumor necrosis factor membrane receptors by activators of protein kinase C

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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

P Scheurich, R Unglaub, B Maxeiner

    Biochemical and Biophysical Research Communications
    |December 15, 1986
    PubMed

    Insights

    Protein kinase C activation rapidly reduces tumor necrosis factor (TNF) membrane receptors on T lymphocytes. This modulation, mediated by protein kinase C, impacts TNF responsiveness by altering receptor binding capacity.

    Area of Science:

    • Immunology
    • Cell Biology
    • Molecular Signaling

    Background:

    • Tumor necrosis factor (TNF) plays a critical role in immune responses and inflammation.
    • Membrane receptors are crucial for cellular communication and signal transduction.
    • T lymphocytes are key players in adaptive immunity, and their responsiveness is tightly regulated.

    Purpose of the Study:

    • To investigate the effect of protein kinase C (PKC) activation on TNF membrane receptors in activated T lymphocytes.
    • To determine the role of PKC in modulating TNF receptor binding capacity and cellular responsiveness.

    Main Methods:

    • Activated T lymphocytes were treated with various PKC activators, including phorbol 12-myristate 13-acetate (PMA), calcium ionophore A 23187, and 1-oleyl-2-acetyl glycerol.
    • Down-regulation of TNF membrane receptors was assessed by measuring binding capacity over time.
    • The effect of a PKC inhibitor (H7) on PMA-induced receptor modulation was evaluated.

    Main Results:

    • Treatment with PMA rapidly down-regulated TNF membrane receptors on activated T lymphocytes, with half-maximal loss of binding capacity observed within 2 minutes.
    • Similar receptor modulation was induced by A 23187 and 1-oleyl-2-acetyl glycerol, suggesting a PKC-dependent mechanism.
    • 1,2-diolein and dibutyryl cAMP were ineffective in modulating TNF receptor binding.
    • The PKC inhibitor H7 antagonized the phorbol ester-induced TNF receptor modulation.

    Conclusions:

    • Protein kinase C plays a significant role in regulating TNF responsiveness in T lymphocytes.
    • PKC activation leads to rapid down-regulation of TNF membrane receptors, thereby altering TNF binding capacity.
    • This modulation may occur through direct phosphorylation of specific receptor proteins.

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