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

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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.
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Date: 3-Sep-2010
Online since: 2014-05-02T08:44:26Z
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
Journal: The Journal of Immunology
Volume: 185
Issue: 7
Start page: 4439
End page: 4445
Copyright (published version): 2010 The American Association of Immunologists
Keywords: NF-κBCO2 Sensing
DOI: 10.4049/jimmunol.1000701
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection

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