TUMOR NECROSIS FACTOR-ALPHA-INDUCED CELL-KILLING AND ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B ARE UNCOUPLED IN L929 CELLS

The induction of transcription factor NF-kappa B has been shown to cou nteract tumor necrosis factor (TNF)-alpha-induced cell death in variou s cell types. In this study, we investigated the role of NF-kappa B fo r TNF-alpha-triggered cell death in the widely used mouse cell line L9 29 by various approaches. Inhibition of the mitochondrial permeability transition by bongkrekic acid impaired TNF-alpha-induced cell death w ithout affecting the activity of NF-kappa B. The reduction of NF-kappa B-mediated gene expression by the synthetic steroid dexamethasone was associated with a decrease in TNF-alpha-mediated cell killing, sugges ting that NF-KB does not protect L929 cells from TNF-alpha-induced cel l death. This concept was reinforced by experiments employing L929 cel l lines stably overexpressing a transdominant negative form of I kappa B-alpha. These cell lines were unable to activate NF-kappa B and to i nducibly express the IL-6 gene, but they showed the same susceptibilit y toward TNF-alpha-mediated cell death as L929 wild-type cells.