Article: article from journal or magazin.
TWEAK can induce cell death via endogenous TNF and TNF receptor 1.
European Journal of Immunology
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.
Antigens, CD/physiology, Apoptosis/drug effects, Apoptosis/physiology, Apoptosis Regulatory Proteins, Base Sequence, Carrier Proteins/genetics, Carrier Proteins/pharmacology, Cell Line, 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
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