Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors

FEBS Letters

Fiers, Walter²  Grell, Matthias¹  Clauss, Matthias³  Fangmann, Carmen³  Scheurich, Peter¹  Risau, Werner³ 

[1] Institut für Zellbiologie und Immunologie, Universität Stuttgart, 70569 Stuttgart, Germany;Laboratory of Molecular Biology, University of Ghent, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium;Abteilung für Molekulare Zellbiologie, Max-Planck-Institut für Physiologische und Klinische Forschung, 61231 Bad Nauheim, Germany

关键词: Receptor;    Tumor necrosis factor;    Vascular endothelial growth factor;    Synergistic induction;    Tissue factor;    TNF;    tumor necrosis factor;    TNFR;    tumor necrosis factor receptor;    VEGF;    vascular endothelial growth factor;   

DOI  :  10.1016/0014-5793(96)00690-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tissue factor expression on the surface of endothelial cells can be induced by tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) in a synergistic manner. We have investigated the role of the two different TNF receptors for this synergy. Firstly, stimulation of the 60 kDa TNF receptor (TNFR60) by a mutant of TNF specific for TNFR60 induced responses comparable to wild-type TNF. In contrast, stimulation of TNFR80 by a TNFR80-specific TNF mutein did not result in enhancement of tissue factor expression even in the presence of a suboptimal TNFR60 triggering. Secondly, we tested neutralizing TNF receptor antibodies for inhibition of tissue factor synthesis induced by VEGF and TNF. A TNFR60-specific antibody inhibited tissue factor production over a broad range of TNF concentrations, indicating an essential role of TNFR60 in the TNF/VEGF synergy. In contrast, blocking of TNF binding to TNFR80 strongly inhibited TNF-induced tissue factor expression at low, but less pronounced at high, TNF concentrations. In conclusion, these data are in agreement with a model in which TNFR80 participates in the synergy between VEGF and low concentrations of soluble TNF by passing the ligand to the signalling TNFR60.

【 授权许可】

Unknown