TNF-alpha suppresses the PDGF beta-receptor kinase

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C Molander1, A Kallin, H Izumi

  • 1Department of Anatomy and Cell Biology, Göteborg University, Gothenburg, Sweden.

Experimental Cell Research
|July 27, 2000
PubMed

Insights

Tumor necrosis factor-alpha (TNF-alpha) suppresses platelet-derived growth factor beta-receptor (PDGF beta-receptor) signaling by reducing receptor phosphorylation. This finding impacts understanding of cellular proliferation and inflammatory responses.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Immunology

Background:

  • Platelet-derived growth factor (PDGF) and tumor necrosis factor-alpha (TNF-alpha) are key inflammatory mediators with often opposing functions.
  • TNF-alpha is known to inhibit PDGF beta-receptor signaling pathways.

Purpose of the Study:

  • To investigate the mechanism by which TNF-alpha attenuates PDGF beta-receptor signaling.
  • To elucidate the impact of TNF-alpha on PDGF-induced fibroblast proliferation.

Main Methods:

  • Mouse 3T3 L1 fibroblasts were pretreated with TNF-alpha before PDGF-BB stimulation.
  • Analysis included PDGF binding assays, receptor quantification, in vitro kinase assays, and in vivo phosphorylation studies using ortho-phosphate labeling.
  • Two-dimensional mapping and phosphoamino acid analysis were employed to assess receptor phosphorylation.

Main Results:

  • TNF-alpha pretreatment significantly reduced the proliferative response of fibroblasts to PDGF.
  • TNF-alpha did not alter PDGF-BB binding or total PDGF beta-receptor levels.
  • Crucially, TNF-alpha decreased both in vitro and in vivo phosphorylation of the PDGF beta-receptor, affecting all known tyrosine residues.

Conclusions:

  • TNF-alpha effectively suppresses PDGF beta-receptor signaling, leading to diminished cellular proliferation.
  • The inhibitory effect occurs downstream of receptor binding and involves reduced receptor phosphorylation.
  • The precise molecular mechanism underlying this suppression warrants further investigation.

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