An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death
- Creators
- Beg, Amer A,
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Baltimore, David
Abstract
Studies on mice deficient in nuclear factor kappa B (NF-κB) subunits have shown that this transcription factor is important for lymphocyte responses to antigens and cytokine-inducible gene expression. In particular, the RelA (p65) subunit is required for induction of tumor necrosis factor-α (TNF-α)-dependent genes. Treatment of RelA-deficient (RelA^(−/−)) mouse fibroblasts and macrophages with TNF-α resulted in a significant reduction in viability, whereas RelA^(+/+) cells were unaffected. Cytotoxicity to both cell types was mediated by TNF receptor 1. Reintroduction of RelA into RelA^(−/−) fibroblasts resulted in enhanced survival, demonstrating that the presence of RelA is required for protection from TNF-α. These results have implications for the treatment of inflammatory and proliferative diseases.
Additional Information
© 1996 American Association for the Advancement of Science. 6 August 1996; accepted 2 October 1996. We thank L. Herzenberg (Stanford University) for the plasmid pON 405, A. Gifford for technical assistance, and members of our laboratory for discussions and comments. A.A.B. was supported by a Concern Il-Cancer Research Institute Fellowship. D.B. is an American Cancer Society Research Professor. Supported by a grant from the Amgen Corporation.Additional details
- Alternative title
- An Essential Role for NF-kappa B in Preventing TNF-alpha -Induced Cell Death
- Eprint ID
- 102738
- DOI
- 10.1126/science.274.5288.782
- Resolver ID
- CaltechAUTHORS:20200422-151000419
- Concern Il-Cancer Research Institute
- American Cancer Society
- Amgen
- Created
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2020-04-22Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field