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J Biol Chem, Vol. 273, Issue 29, 18117-18121, July 17, 1998

Tumor Necrosis Factor--induced Cell Killing and Activation of Transcription Factor NF-B Are Uncoupled in L929 Cells

From the Department of Immunochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

The induction of transcription factor NF-B has been shown to counteract tumor necrosis factor (TNF)--induced cell death in various cell types. In this study, we investigated the role of NF-B for TNF--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--induced cell death without affecting the activity of NF-B. The reduction of NF-B-mediated gene expression by the synthetic steroid dexamethasone was associated with a decrease in TNF--mediated cell killing, suggesting that NF-B does not protect L929 cells from TNF--induced cell death. This concept was reinforced by experiments employing L929 cell lines stably overexpressing a transdominant negative form of IB-. These cell lines were unable to activate NF-B and to inducibly express the IL-6 gene, but they showed the same susceptibility toward TNF--mediated cell death as L929 wild-type cells.

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