Abstract

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.

Highlights

  • The cytokine tumor necrosis factor (TNF)-␣1 plays a pivotal role in a variety of inflammatory, immunological, and pathological processes

  • We investigated the role of NF-␬B for TNF-␣-triggered cell death in the widely used mouse cell line L929 by various approaches

  • We demonstrated that TNF-␣-triggered cell killing and activation of transcription factor NF-␬B are uncoupled in L929 cells

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Summary

Introduction

The cytokine TNF-␣1 plays a pivotal role in a variety of inflammatory, immunological, and pathological processes. Inhibition of the mitochondrial permeability transition by bongkrekic acid impaired TNF-␣-induced cell death without affecting the activity of NF-␬B. 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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