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 and Mechanisms
Pages range:
169-181
Volume number:
8
Issue number:
2
Start page:
169
End page:
181
Number of pages:
13
ISSN:
1754-8403

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.


Keywords
Drosophila, HIF-1, Hypoxia, IKK, inflammation, NF-kappa B


Authors/Editors

Last updated on 2019-25-07 at 19:32