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A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death

Binding sites for the nuclear factor (NF)-κB transcription factor have been identified within control regions of many genes involved in inflammatory and immune responses. Such κB sites are often found adjacent to those of interferon (IFN)-γ–inducible transcription factors, suggesting a requirement f...

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Autores principales: Ouaaz, Fateh, Li, Ming, Beg, Amer A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193051/
https://www.ncbi.nlm.nih.gov/pubmed/10075983
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author Ouaaz, Fateh
Li, Ming
Beg, Amer A.
author_facet Ouaaz, Fateh
Li, Ming
Beg, Amer A.
author_sort Ouaaz, Fateh
collection PubMed
description Binding sites for the nuclear factor (NF)-κB transcription factor have been identified within control regions of many genes involved in inflammatory and immune responses. Such κB sites are often found adjacent to those of interferon (IFN)-γ–inducible transcription factors, suggesting a requirement for multiple signaling pathways for gene regulation. Using fibroblasts from RelA (p65)-deficient mice generated by gene targeting, we have investigated the role of this subunit of NF-κB in gene activation by microbial lipopolysaccharide, tumor necrosis factor α, and in possible synergism with the IFN-γ–signaling pathway. Our results indicate not only that RelA is required for activation of key genes involved in adaptive (acquired) immune responses, including major histocompatibility complex class I, CD40, and the Fas death receptor, but also that both NF-κB–inducing signals and IFN-γ are necessary for maximal activation. In contrast, neutrophil-specific chemokine genes KC and MIP-2, which can function as nonspecific mediators in innate immune responses, were strongly induced by RelA in the absence of IFN-γ. Our results show that RelA plays a critical role in activation of immune system genes in response to nonspecific stimuli and demonstrate a novel proapoptotic function for this protein in Fas-induced cell death.
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spelling pubmed-21930512008-04-16 A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death Ouaaz, Fateh Li, Ming Beg, Amer A. J Exp Med Brief Definitive Reports Binding sites for the nuclear factor (NF)-κB transcription factor have been identified within control regions of many genes involved in inflammatory and immune responses. Such κB sites are often found adjacent to those of interferon (IFN)-γ–inducible transcription factors, suggesting a requirement for multiple signaling pathways for gene regulation. Using fibroblasts from RelA (p65)-deficient mice generated by gene targeting, we have investigated the role of this subunit of NF-κB in gene activation by microbial lipopolysaccharide, tumor necrosis factor α, and in possible synergism with the IFN-γ–signaling pathway. Our results indicate not only that RelA is required for activation of key genes involved in adaptive (acquired) immune responses, including major histocompatibility complex class I, CD40, and the Fas death receptor, but also that both NF-κB–inducing signals and IFN-γ are necessary for maximal activation. In contrast, neutrophil-specific chemokine genes KC and MIP-2, which can function as nonspecific mediators in innate immune responses, were strongly induced by RelA in the absence of IFN-γ. Our results show that RelA plays a critical role in activation of immune system genes in response to nonspecific stimuli and demonstrate a novel proapoptotic function for this protein in Fas-induced cell death. The Rockefeller University Press 1999-03-15 /pmc/articles/PMC2193051/ /pubmed/10075983 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Ouaaz, Fateh
Li, Ming
Beg, Amer A.
A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title_full A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title_fullStr A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title_full_unstemmed A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title_short A Critical Role for the RelA Subunit of Nuclear Factor κB in Regulation of Multiple Immune-response Genes and in Fas-induced Cell Death
title_sort critical role for the rela subunit of nuclear factor κb in regulation of multiple immune-response genes and in fas-induced cell death
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193051/
https://www.ncbi.nlm.nih.gov/pubmed/10075983
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