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Updated: Aug 7, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method

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Downregulation of tumor necrosis factor (TNF) sensitivity via modulation of TNF binding capacity by protein kinase C

R Unglaub1, B Maxeiner, B Thoma

  • 1Klinische Arbeitsgruppe BRWTI, Max-Planck-Gesellschaft, Göttingen, Federal Republic of Germany.

The Journal of Experimental Medicine
|December 1, 1987
PubMed

Insights

Protein kinase C activators downregulate tumor necrosis factor alpha (TNF-alpha) binding capacity by altering receptor affinity, not internalization. This regulation impacts cellular sensitivity to TNF-alpha, affecting cytotoxicity and immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Tumor necrosis factor alpha (TNF-alpha) is a key cytokine in inflammation and immunity.
  • The TNF-alpha receptor (TNFR) binding capacity influences cellular responses to TNF-alpha.
  • Protein kinase C (PKC) is involved in various cellular signaling pathways.

Purpose of the Study:

  • To investigate how protein kinase C (PKC) activators regulate the binding capacity of the human tumor necrosis factor alpha (TNF-alpha) receptor.
  • To elucidate the mechanism by which PKC affects TNF-alpha receptor binding and subsequent cellular sensitivity.

Main Methods:

  • Studied the effect of PKC activators (PMA, OAG) on TNF-alpha binding capacity in various human cell lines.
  • Assessed TNF-alpha receptor complex internalization and protein shedding.
  • Evaluated TNF-alpha sensitivity through cytotoxicity assays and HLA class II antigen expression.

Main Results:

  • PMA and OAG rapidly downregulated TNF-alpha binding capacity in normal and malignant cells.
  • PKC activation controlled TNF-alpha receptor ligand affinity, likely via phosphorylation, independent of internalization or shedding.
  • Downregulation of TNF-alpha binding correlated with reduced TNF-alpha sensitivity, including decreased cytotoxicity and inhibited HLA class II antigen expression.

Conclusions:

  • Protein kinase C activation regulates TNF-alpha receptor binding affinity, serving as a cellular mechanism controlling TNF-alpha responsiveness.
  • PKC-mediated regulation of TNF-alpha binding capacity is directly linked to cellular sensitivity to TNF-alpha.
  • Restoration of TNF-binding capacity upon PKC inhibition confirms the linkage between receptor expression and TNF sensitivity.

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