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The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation.
- Source :
-
Nature immunology [Nat Immunol] 2011 Nov 20; Vol. 13 (1), pp. 29-34. Date of Electronic Publication: 2011 Nov 20. - Publication Year :
- 2011
-
Abstract
- The NADPH oxidase activity of phagocytes and its generation of reactive oxygen species (ROS) is critical for host defense, but ROS overproduction can also lead to inflammation and tissue injury. Here we report that TRPM2, a nonselective and redox-sensitive cation channel, inhibited ROS production in phagocytic cells and prevented endotoxin-induced lung inflammation in mice. TRPM2-deficient mice challenged with endotoxin (lipopolysaccharide) had an enhanced inflammatory response and diminished survival relative to that of wild-type mice challenged with endotoxin. TRPM2 functioned by dampening NADPH oxidase-mediated ROS production through depolarization of the plasma membrane in phagocytes. As ROS also activate TRPM2, our findings establish a negative feedback mechanism for the inactivation of ROS production through inhibition of the membrane potential-sensitive NADPH oxidase.
- Subjects :
- Animals
Calcium metabolism
Inflammation genetics
Inflammation pathology
Lung Diseases genetics
Lung Diseases metabolism
Lung Diseases pathology
Membrane Potentials
Mice
Mice, Inbred C57BL
Mice, Knockout
Oxidation-Reduction
TRPM Cation Channels deficiency
TRPM Cation Channels genetics
Inflammation metabolism
Phagocytes metabolism
Reactive Oxygen Species metabolism
TRPM Cation Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 22101731
- Full Text :
- https://doi.org/10.1038/ni.2171