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Title: NF-kappa B Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells
Authors: Cummins, Eoin P
Oliver, Kathryn M
Lenihan, Colin R
Fitzpatrick, Susan F
BRUENING ROSSOW, Ulrike
Scholz, Carsten C
Slattery, Craig
Leonard, Martin O
McLoughlin, Paul
Taylor, Cormac T # ×
Issue Date: Oct-2010
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:185 issue:7 pages:4439-4445
Abstract: Molecular O-2 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 O-2 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-kappa B pathway. IKK alpha, a central regulatory component of NF-kappa B, 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. The Journal of Immunology, 2010, 185: 4439-4445.
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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