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

Abstract:

: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.

journal_name

Eur J Immunol

authors

Schneider P,Schwenzer R,Haas E,Mühlenbeck F,Schubert G,Scheurich P,Tschopp J,Wajant H

doi

10.1002/(SICI)1521-4141(199906)29:06<1785::AID-IMM

keywords:

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

1785-92

issue

6

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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