Evidence for a Synergistic Role of Two Types of Human Tumor Necrosis Factor Receptors for the Ligand-Dependent Activation of the Nuclear Transcription Factor NF-κB

1998 ◽  
Vol 18 (2) ◽  
pp. 117-123 ◽  
Author(s):  
RINEE MUKHERJEE ◽  
SANJAYA SINGH ◽  
MADAN M. CHATURVEDI ◽  
BHARAT B. AGGARWAL
1990 ◽  
Vol 172 (5) ◽  
pp. 1517-1520 ◽  
Author(s):  
M R Shalaby ◽  
A Sundan ◽  
H Loetscher ◽  
M Brockhaus ◽  
W Lesslauer ◽  
...  

The present study was undertaken to further characterize the interaction of monoclonal antibodies (mAbs) against tumor necrosis factor (TNF) receptors with different targets, and to assess their ability to influence TNF effects on U937 and human endothelial cell (HEC) functions. Actions of recombinant TNF-alpha on U937 and HEC were effectively inhibited by Htr-5 and Utr-1, and to a greater extent by a combination of both mAbs. These observations indicate that TNF interaction with antigenically different components of membrane receptors (p55 and p75) represents a crucial step in transduction of signals for TNF toxicity against U937 and TNF activation of HEC functions.


1992 ◽  
Vol 176 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
P Vandenabeele ◽  
W Declercq ◽  
D Vercammen ◽  
M Van de Craen ◽  
J Grooten ◽  
...  

We investigated the biological role of the human tumor necrosis factor p75 (hTNF-R75), making use of the species specificity of TNF responses in murine (m) T cell lines. Several TNF-mediated activities on mouse T cells, such as cytokine induction or proliferation, showed a 100-500-fold difference in specific biological activity between mTNF and hTNF. After transfection of hTNF-R75 cDNA in a rat/mouse T cell hybridoma (PC60), however, the 100-fold lower specific biological activity of hTNF was converted to the same specific biological activity as mTNF. The TNF-mediated induction of granulocyte/macrophage colony-stimulating factor was strongly synergized by the addition of interleukin 1. In the presence of the latter cytokine, ligand-competing monoclonal antibodies against hTNF-R75 (utr-1, utr-2, utr-3) were agonistic on transfected PC60 cells. This agonistic activity was further enhanced by crosslinking with sheep anti-murine immunoglobulin antibodies. These data provide direct evidence for a functional role of TNF-R75, without ligand-dependent TNF-R55 involvement, in the induction of cytokine secretion in T cells.


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