Type

Journal Article

Authors

Cormac T. Taylor
Eoin P. Cummins
Padraic G Fallon
Katherine Howell
John F Garvey
Colin R. Lenihan
William M Gallagher
Aisling O'Connor
Annette Byrne
Carsten C. Scholz
and 4 others

Subjects

Biochemistry

Topics
gene expression regulation hela cells female genetics immunology metabolism signal transduction biosynthesis caco 2 cells myocardium male mice inbred c57bl physiology pathology anoxia cyclooxygenase 2 ptgs2 protein human hypoxia inducible factor 1 alpha subunit inflammation mediators animals nf kappa b lung mice hif1a protein human cells cultured mice transgenic antagonists inhibitors humans

An intact canonical NF-κB pathway is required for inflammatory gene expression in response to hypoxia. (2010)

Abstract Hypoxia is a feature of the microenvironment in a number of chronic inflammatory conditions due to increased metabolic activity and disrupted perfusion at the inflamed site. Hypoxia contributes to inflammation through the regulation of gene expression via key oxygen-sensitive transcriptional regulators including the hypoxia-inducible factor (HIF) and NF-κB. Recent studies have revealed a high degree of interdependence between HIF and NF-κB signaling; however, the relative contribution of each to hypoxia-induced inflammatory gene expression remains unclear. In this study, we use transgenic mice expressing luciferase under the control of NF-κB to demonstrate that hypoxia activates NF-κB in the heart and lungs of mice in vivo. Using small interfering RNA targeted to the p65 subunit of NF-κB, we confirm a unidirectional dependence of hypoxic HIF-1α accumulation upon an intact canonical NF-κB pathway in cultured cells. Cyclooxygenase-2 and other key proinflammatory genes are transcriptionally induced by hypoxia in a manner that is both HIF-1 and NF-κB dependent, and in mouse embryonic fibroblasts lacking an intact canonical NF-κB pathway, there is a loss of hypoxia-induced inflammatory gene expression. Finally, under conditions of hypoxia, HIF-1α and the p65 subunit of NF-κB directly bind to the cyclooxygenase-2 promoter. These results implicate an essential role for NF-κB signaling in inflammatory gene expression in response to hypoxia both through the regulation of HIF-1 and through direct effects upon target gene expression.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Cormac T. Taylor, Eoin P. Cummins, Padraic G Fallon, Katherine Howell, John F Garvey, Colin R. Lenihan, William M Gallagher, Aisling O'Connor, Annette Byrne, Carsten C. Scholz and 4 others

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
3
Padraic Fallon
Trinity College Dublin
Total Publications: 154
 
4
Colin R. Lenihan
University College Dublin
Total Publications: 6
 
5
William M Gallagher
University College Dublin
Total Publications: 148
 
6
Annette T Byrne
Royal College of Surgeons in Ireland
Total Publications: 41
 
7
Carsten C Scholz
University College Dublin
Total Publications: 21