A decision between life and death during TNF-alpha-induced signaling

J Clin Immunol. 2002 Jul;22(4):185-94. doi: 10.1023/a:1016089607548.


Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, exerts its biological activity by signaling via its two receptors, TNF-RI and TNF-RII, and by activating NF-kappaB. NF-kappaB is essential for survival of many cell types; however, TNF-alpha also induces cell death. In this article, both the survival and cell death signaling by TNF-alpha and the role of caspases in turning off NF-kappaB survival signal are reviewed. Furthermore, a role of DAP kinase in TNF-induced apoptosis is discussed. Finally, the molecular basis of the effect of age on TNF-alpha-induced apoptosis in human T cells is reviewed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging / immunology
  • Antigens, CD / metabolism
  • Apoptosis / immunology*
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Caspases / metabolism
  • Cell Survival / immunology*
  • Cell Survival / physiology
  • Death-Associated Protein Kinases
  • Humans
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Models, Immunological
  • NF-kappa B / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Caspases