Tumor necrosis factor-α-induced cell killing and activation of transcription factor NF-κB are uncoupled in 1929 cells

Abstract

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