Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM2

Title: The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation.

Authors: Anke Di, Xiao-Pei Gao, Feng Qian, Takeshi Kawamura, Jin Han, Claudie Hecquet, Richard D Ye, Stephen M Vogel, Asrar B Malik

Journal, date & volume: Nat. Immunol., 2012 Jan , 13, 29-34

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22101731

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.