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

Files in This Item:
File Description SizeFormat 
Paper96.pdf2.64 MBAdobe PDFDownload
Title: NF-B Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells
Authors: Cummins, Eoin P.
Oliver, K. M.
Lenihan, Colin R.
et al.
Permanent link: http://hdl.handle.net/10197/5576
Date: 3-Sep-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.
Type of material: Journal Article
Publisher: The American Association of Immunologists
Copyright (published version): 2010 The American Association of Immunologists
Keywords: NF-κB;CO2 Sensing
DOI: 10.4049/jimmunol.1000701
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection

Show full item record

SCOPUSTM   
Citations 5

45
Last Week
2
Last month
checked on Jun 23, 2018

Page view(s) 50

36
checked on May 25, 2018

Download(s) 50

130
checked on May 25, 2018

Google ScholarTM

Check

Altmetric


This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.