title: The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation.
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.
authors.affiliation: Department of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois, Chicago, Illinois, USA.
authors.forename: Anke
authors.initials: A
authors.lastname: Di
authors.forename: Xiao-Pei
authors.initials: XP
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Claudie
authors.initials: C
authors.lastname: Hecquet
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ye
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vogel
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; D002118:Calcium
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