NF-B Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells
|Title:||NF-B Links CO2 Sensing to Innate Immunity and Inflammation in Mammalian Cells||Authors:||Cummins, Eoin P.
Oliver, K. M.
Lenihan, Colin R.
|Permanent link:||http://hdl.handle.net/10197/5576||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-κB; CO2 Sensing||DOI:||10.4049/jimmunol.1000701||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
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