Tumor Necrosis Factor-α-induced Cell Killing and Activation of Transcription Factor NF-κB Are Uncoupled in L929 Cells*
- Steffen P. Hehner,
- Thomas G. Hofmann,
- Frank Ratter,
- Andreas Dumont,
- Wulf Dröge and
- M. Lienhard Schmitz‡
- From the Department of Immunochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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.
Footnotes
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↵* This work was supported by a European Biomed-2 grant (to M. L. S.), by the German-Israeli Cooperation in Cancer Research, sponsored by the Deutsches Krebsforschungszentrum, and by the Ministry of Science of Israel (to S. P. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 49-6221-423725; Fax: 49-6221-423746; E-mail:L.Schmitz{at}DKFZ-Heidelberg.de.
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↵1 The abbreviations used are: TNF, tumor necrosis factor; BA, bongkrekic acid; DEX, dexamethasone; EMSA, electrophoretic mobility shift assay; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide.
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- Received May 6, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
