HIF-1α restricts NF-κB dependent gene expression to control innate immunity signals
Copyright policy )HIF-1α restricts NF-κB dependent gene expression to control innate immunity signals
Abstract Hypoxia and inflammation are intimately linked. It is known that NF-κB regulates the HIF system but little is known about how HIF regulates NF-κB. Here, we show that HIF-1α represses NF-κB dependent gene expression. HIF-1α depletion results in increased NF-κB transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1α depletion enhanced the NF-κB response and this required not only the TAK-IKK complex, but also CDK6. Loss of HIF-1α results in an increased angiogenic response in mammalian cancer cells and increased mortality in Drosophila following infection. These results indicate that HIF-1α is required to restrain the NF-κB response, and thus prevents excessive and damaging pro-inflammatory responses.
- University of Dundee United Kingdom
- Wellcome Trust United Kingdom
570, Neovascularization, Physiologic, NF-κB, Cell Line, name=Immunology and Microbiology (miscellaneous), /dk/atira/pure/subjectarea/asjc/2800/2801, /dk/atira/pure/subjectarea/asjc/2700/2701, name=General Biochemistry,Genetics and Molecular Biology, Pathology, RB1-214, Animals, Drosophila Proteins, Humans, /dk/atira/pure/subjectarea/asjc/2400/2401, name=Medicine (miscellaneous), Hypoxia, Escherichia coli Infections, Inflammation, Mammals, /dk/atira/pure/subjectarea/asjc/1300/1300, name=Neuroscience (miscellaneous), IKK, HIF-1, R, NF-kappa B, Cyclin-Dependent Kinase 6, Hypoxia-Inducible Factor 1, alpha Subunit, MAP Kinase Kinase Kinases, Survival Analysis, Immunity, Innate, I-kappa B Kinase, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, Gene Knockdown Techniques, Medicine, Drosophila, Nf-κb, Research Article, Signal Transduction
570, Neovascularization, Physiologic, NF-κB, Cell Line, name=Immunology and Microbiology (miscellaneous), /dk/atira/pure/subjectarea/asjc/2800/2801, /dk/atira/pure/subjectarea/asjc/2700/2701, name=General Biochemistry,Genetics and Molecular Biology, Pathology, RB1-214, Animals, Drosophila Proteins, Humans, /dk/atira/pure/subjectarea/asjc/2400/2401, name=Medicine (miscellaneous), Hypoxia, Escherichia coli Infections, Inflammation, Mammals, /dk/atira/pure/subjectarea/asjc/1300/1300, name=Neuroscience (miscellaneous), IKK, HIF-1, R, NF-kappa B, Cyclin-Dependent Kinase 6, Hypoxia-Inducible Factor 1, alpha Subunit, MAP Kinase Kinase Kinases, Survival Analysis, Immunity, Innate, I-kappa B Kinase, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, Gene Knockdown Techniques, Medicine, Drosophila, Nf-κb, Research Article, Signal Transduction
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