scholarly journals Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFα)-induced apoptosis through two distinct pathways involving NF-κB downregulation and Fas-mediated formation of death inducing signaling complex

2008 ◽  
Vol 123 (9) ◽  
pp. 2204-2212 ◽  
Author(s):  
Vivek Sharma ◽  
Richa Tewari ◽  
Ugir Hossain Sk ◽  
Christy Joseph ◽  
Ellora Sen
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Glioblastoma Cells ◽  
Signaling Complex ◽  
Induced Apoptosis ◽  
Necrosis Factor

scholarly journals Distinct Signaling Pathways in TRAIL- versus Tumor Necrosis Factor-Induced Apoptosis

2006 ◽  
Vol 26 (21) ◽  
pp. 8136-8148 ◽  
Author(s):  
Zhaoyu Jin ◽  
Wafik S. El-Deiry
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Caspase 8 ◽  
Hairpin Rna ◽  
Complex Ii ◽  
Signaling Complex ◽  
Fas L ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Trimeric tumor necrosis factor (TNF) binding leads to recruitment of TRADD to TNFR1. In current models, TRADD recruits RIP, TRAF2, and FADD to activate NF-κB, Jun N-terminal protein kinase (JNK), and apoptosis. Using stable short-hairpin RNA (shRNA) knockdown (KD) cells targeting these adaptors, TNF death-inducing signaling complex immunoprecipitation demonstrates competitive binding of TRADD and RIP to TNFR1, whereas TRAF2 recruitment requires TRADD. Analysis of KD cells indicates that FADD is necessary for Fas-L- or TRAIL- but not TNF-induced apoptosis. Interestingly, TRADD is dispensable, while RIP is required for TNF-induced apoptosis in human tumor cells. TRADD is required for c-Jun phosphorylation upon TNF exposure. RIP KD abrogates formation of complex II following TNF exposure, whereas TRADD KD allows efficient RIP-caspase 8 association. Treatment with TRAIL also induces formation of a complex II containing FADD, RIP, IKKα, and caspase 8 and 10, leading to activation of caspase 8. Our data suggest that TNF triggers apoptosis in a manner distinct from that of Fas-L or TRAIL.

scholarly journals Macrophage-dependent Apoptosis of CD4+ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor

1997 ◽  
Vol 185 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Andrew D. Badley ◽  
David Dockrell ◽  
Margaret Simpson ◽  
Ron Schut ◽  
David H. Lynch ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
T Lymphocytes ◽  
Cd4 T Cells ◽  
Tumor Necrosis ◽  
Human Macrophages ◽  
Infected Cells ◽  
Induced Apoptosis ◽  
Antigen Presenting ◽  
Necrosis Factor

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

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