HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals

Bandarra, D., Biddlestone, J., Mudie, S., Müller, H.-A. J. and Rocha, S. (2015) HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Disease Models and Mechanisms, 8(2), pp. 169-181. (doi: 10.1242/dmm.017285) (PMID:25510503) (PMCID:PMC4314782)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biddlestone, Dr John
• Authors: Bandarra, D., Biddlestone, J., Mudie, S., Müller, H.-A. J., and Rocha, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Disease Models and Mechanisms
• Publisher: Company of Biologists
• ISSN: 1754-8403
• ISSN (Online): 1754-8411
• Published Online: 15 December 2014
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Disease Models and Mechanisms 8(2):169-181
• Publisher Policy: Reproduced under a Creative Commons License