An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.
Studies on mice deficient in nuclear factor kappa B (NF-kappaB) 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-alpha (TNF-alpha)-dependent genes. Treatment of RelA-deficient (RelA-/-) mouse fibroblasts and macrophages with TNF-alpha 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-alpha. These results have implications for the treatment of inflammatory and proliferative diseases.
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Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Baltimore
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D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D051996:Transcription Factor RelA; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
D015703:Antigens, CD; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha