Journal article
HIF-1 alpha restricts NF-kappa B-dependent gene expression to control innate immunity signals
Publication Details
Authors: | Bandarra, D.; Biddlestone, J.; Mudie, S.; Müller, H.; Rocha, S. |
Publisher: | COMPANY OF BIOLOGISTS LTD |
Publication year: | 2015 |
Journal: | Disease Models & Mechanisms |
Pages range : | 169-181 |
Volume number: | 8 |
Issue number: | 2 |
Start page: | 169 |
End page: | 181 |
Number of pages: | 13 |
ISSN: | 1754-8403 |
DOI-Link der Erstveröffentlichung: |
Abstract
Hypoxia and inflammation are intimately linked. It is known that nuclear factor.B (NF-kappa B) regulates the hypoxia-inducible factor (HIF) system, but little is known about how HIF regulates NF-kappa B. Here, we show that HIF-1 alpha represses NF-kappa B-dependent gene expression. HIF1 alpha depletion results in increased NF-kappa B transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1 alpha depletion enhances the NF-kappa B response, and this required not only the TAK-IKK complex, but also CDK6. Loss of HIF-1 alpha results in an increased angiogenic response in mammalian cancer cells and increased mortality in Drosophila following infection. These results indicate that HIF-1 alpha is required to restrain the NF-kappa B response, and thus prevents excessive and damaging proinflammatory responses.
Hypoxia and inflammation are intimately linked. It is known that nuclear factor.B (NF-kappa B) regulates the hypoxia-inducible factor (HIF) system, but little is known about how HIF regulates NF-kappa B. Here, we show that HIF-1 alpha represses NF-kappa B-dependent gene expression. HIF1 alpha depletion results in increased NF-kappa B transcriptional activity both in mammalian cells and in the model organism Drosophila melanogaster. HIF-1 alpha depletion enhances the NF-kappa B response, and this required not only the TAK-IKK complex, but also CDK6. Loss of HIF-1 alpha results in an increased angiogenic response in mammalian cancer cells and increased mortality in Drosophila following infection. These results indicate that HIF-1 alpha is required to restrain the NF-kappa B response, and thus prevents excessive and damaging proinflammatory responses.
Keywords
Drosophila, HIF-1, Hypoxia, IKK, inflammation, NF-kappa B
