Tumor necrosis factor-alpha-induced cell killing and activation of transcription factor NF-kappaB are uncoupled in L929 cells.
The induction of transcription factor NF-kappaB has been shown to counteract tumor necrosis factor (TNF)-alpha-induced cell death in various cell types. In this study, we investigated the role of NF-kappaB for TNF-alpha-triggered cell death in the widely used mouse cell line L929 by various approaches. Inhibition of the mitochondrial permeability transition by bongkrekic acid impaired TNF-alpha-induced cell death without affecting the activity of NF-kappaB. The reduction of NF-kappaB-mediated gene expression by the synthetic steroid dexamethasone was associated with a decrease in TNF-alpha-mediated cell killing, suggesting that NF-kappaB does not protect L929 cells from TNF-alpha-induced cell death. This concept was reinforced by experiments employing L929 cell lines stably overexpressing a transdominant negative form of IkappaB-alpha. These cell lines were unable to activate NF-kappaB and to inducibly express the IL-6 gene, but they showed the same susceptibility toward TNF-alpha-mediated cell death as L929 wild-type cells.
Hehner
S P
SP
Department of Immunochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Hofmann
T G
TG
Ratter
F
F
Dumont
A
A
Dröge
W
W
Schmitz
M L
ML
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001865:Bongkrekic Acid / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D001865:Bongkrekic Acid; D000072000:NF-KappaB Inhibitor alpha; D003907:Dexamethasone