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The redox‐sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation

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Title: The redox‐sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation
Author(s): Di, Anke; Gao, Xiao‐Pei; Qian, Feng; Kawamura, Takeshi; Han, Jin; Hecquet, Claudie; Ye, Richard D; Vogel, Stephen M; Malik, Asrar B
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) showed an enhanced inflammatory response and lower 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.
Issue Date: 2011
Publisher: Nature Publishing Group
Citation Info: Di, A., Gao, X. P., Qian, F., Kawamura, T., Han, J., Hecquet, C., Ye, R. D., Vogel, S. M., & Malik, A. B. 2011. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation. Nature Immunology, 13(1): 29-34. doi:10.1038/ni.2171
Type: Article
Description: © 2011 by Nature Publishing Group, Nature Immunology doi:10.1038/ni.2171
ISSN: 1529-2908
Sponsor: Supported by the Francis Families Foundation (Parker B. Francis Fellowship Program, 2007−2010) and the US National Institutes of Health (P01 HL77806).
Date Available in INDIGO: 2012-08-16

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