HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals
| Autor: | Daniel Bandarra, John Biddlestone, Sharon Mudie, H.-Arno J. Müller, Sonia Rocha |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Disease Models & Mechanisms, Vol 8, Iss 2, Pp 169-181 (2015) |
| Druh dokumentu: | article |
| ISSN: | 1754-8403 1754-8411 04972929 |
| DOI: | 10.1242/dmm.017285 |
| Popis: | Hypoxia and inflammation are intimately linked. It is known that nuclear factor κB (NF-κB) regulates the hypoxia-inducible factor (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 enhances 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. |
| Databáze: | Directory of Open Access Journals |
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