Type

Journal Article

Authors

Cormac T. Taylor
Paul McLoughlin
Martin O Leonard
Craig Slattery
Colin R. Lenihan
Carsten C. Scholz
K. M. Oliver
Ulrike Bruning
Eoin P. Cummins
Susan F. Fitzpatrick

Subjects

Biochemistry

Topics
animals nf kappa b hypoxia inducible factor microscopy fluorescence mice cells cultured reverse transcriptase polymerase chain reaction mammalian innate immunity protein transport mammalian cells innate immunity inflammation humans gene expression regulation gene expression microscopy confocal immunology carbon dioxide nf b signal transduction metabolism i kappa b kinase co2 sensing inflammation physiology blotting western immunity innate b cells

NF-B Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells (2010)

Abstract Molecular O2 and CO2 are the primary substrate and product of aerobic metabolism, respectively. Levels of these physiologic gases in the cell microenvironment vary dramatically both in health and in diseases, such as chronic inflammation, ischemia, and cancer, in which metabolism is significantly altered. The identification of the hypoxia-inducible factor led to the discovery of an ancient and direct link between tissue O2 and gene transcription. In this study, we demonstrate that mammalian cells (mouse embryonic fibroblasts and others) also sense changes in local CO2 levels, leading to altered gene expression via the NF-κB pathway. IKKα, a central regulatory component of NF-κB, rapidly and reversibly translocates to the nucleus in response to elevated CO2. This response is independent of hypoxia-inducible factor hydroxylases, extracellular and intracellular pH, and pathways that mediate acute CO2-sensing in nematodes and flies and leads to attenuation of bacterial LPS-induced gene expression. These results suggest the existence of a molecular CO2 sensor in mammalian cells that is linked to the regulation of genes involved in innate immunity and inflammation.
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Full list of authors on original publication

Cormac T. Taylor, Paul McLoughlin, Martin O Leonard, Craig Slattery, Colin R. Lenihan, Carsten C. Scholz, K. M. Oliver, Ulrike Bruning, Eoin P. Cummins, Susan F. Fitzpatrick

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Paul McLoughlin
University College Dublin
 
3
Craig Slattery
University College Dublin
Total Publications: 27
 
4
Colin R. Lenihan
University College Dublin
Total Publications: 6
 
5
Carsten C Scholz
University College Dublin
Total Publications: 21
 
6
Ulrike Bruning
University College Dublin
Total Publications: 10
 
7
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
8
Susan F. Fitzpatrick
University College Dublin
Total Publications: 9