The cytoprotective effects of tumor necrosis factor are conveyed through tumor necrosis factor receptor-associated

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Updated: Jun 19, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Jana S Burchfield1, Jian-Wen Dong, Yasushi Sakata

  • 1Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Circulation. Heart Failure
|November 3, 2009
PubMed
Abstract

Insights

Tumor necrosis factor (TNF) protects the heart via TRAF2, a key protein. This study shows TNF receptor-associated factor 2 (TRAF2) activation of nuclear factor-kappaB is crucial for this cytoprotective effect in cardiac myocytes.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cellular Signaling

Background:

  • Tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) activate cytoprotective pathways in cardiac cells.
  • TNF receptor-associated factor 2 (TRAF2) is a shared scaffolding protein for both TNFR1 and TNFR2.

Purpose of the Study:

  • To investigate if TNF-mediated cytoprotection in the heart is dependent on TRAF2.
  • To elucidate the role of TRAF2 in cardiac response to ischemia-reperfusion injury.

Main Methods:

  • Cardiac-restricted overexpression of TNF and TRAF2 in mice.
  • Generation of mice deficient in TNFR1, TNFR2, or both.
  • Ex vivo Langendorff apparatus model to induce and assess ischemia-reperfusion injury.
  • Measurement of left ventricular developed pressure, creatine kinase release, and Evans blue dye uptake.
  • Biochemical analysis of signaling pathways, including nuclear factor-kappaB and c-Jun N-terminal kinase.

Main Results:

  • Mice overexpressing TNF showed protection against ischemia-reperfusion injury.
  • Mice lacking both TNFR1 and TNFR2 exhibited exacerbated injury.
  • Mice overexpressing TRAF2 demonstrated significant protection, with reduced injury markers.
  • TRAF2 overexpression led to nuclear factor-kappaB activation but not c-Jun N-terminal kinase activation.

Conclusions:

  • TNF confers cytoprotection in the heart.
  • This protective effect is mediated through TRAF2.
  • TRAF2-dependent cytoprotection involves the activation of nuclear factor-kappaB.

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