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

TY - JOUR

T1 - HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals

AU - Bandarra, Daniel

AU - Biddlestone, John

AU - Mudie, Sharon

AU - Müller, H. -Arno J.

AU - Rocha, Sonia

PY - 2015/2

Y1 - 2015/2

N2 - 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 proinflammatory responses.

AB - 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 proinflammatory responses.

KW - Drosophila

KW - HIF-1

KW - Hypoxia

KW - IKK

KW - Inflammation

KW - Nf-κb

UR - https://www.scopus.com/pages/publications/84922485491

U2 - 10.1242/dmm.017285

DO - 10.1242/dmm.017285

M3 - Article

C2 - 25510503

AN - SCOPUS:84922485491

SN - 1754-8403

VL - 8

SP - 169

EP - 181

JO - Disease Models and Mechanisms (DMM)

JF - Disease Models and Mechanisms (DMM)

IS - 2

ER -