TWEAK can induce cell death via endogenous TNF and TNF receptor 1

Eur J Immunol. 1999 Jun;29(6):1785-92. doi: 10.1002/(SICI)1521-4141(199906)29:06<1785::AID-IMMU1785>3.0.CO;2-U.


TWEAK is a recently cloned novel member of the TNF ligand family. Here we show that soluble TWEAK is sufficient to induce apoptosis in Kym-1 cells within 18 h. TWEAK-induced apoptosis is indirect and is mediated by the interaction of endogenous TNF and TNF receptor (TNFR)1, as each TNFR1-Fc, neutralizing TNF-specific antibodies and TNFR1-specific Fab fragments efficiently antagonize cell death induction. In addition to this indirect mode of action, co-stimulation of Kym-1 cells with TWEAK enhances TNFR1-mediated cell death induction. In contrast to TNF, TWEAK does only modestly activate NF-kappaB or c-jun N-terminal kinase (JNK) in Kym-1 cells. Although TWEAK binding to Kym-1 cells is easily detectable by flow cytometric analysis, we found neither evidence for expression of the recently identified TWEAK receptor Apo3/TRAMP/wsl/DR3/LARD, nor indications for direct interactions of TWEAK with TNFR. Together, these characteristics of TWEAK-induced signaling in Kym-1 cells argue for the existence of an additional, still undefined non-death domain-containing TWEAK receptor in Kym-1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / physiology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Cell Line
  • Cytokine TWEAK
  • Humans
  • NF-kappa B / metabolism
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • Tumor Necrosis Factors


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cytokine TWEAK
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • TNFRSF25 protein, human
  • TNFSF12 protein, human
  • Tumor Necrosis Factor-alpha
  • Tumor Necrosis Factors