Journal article
The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation
Nature immunology, Vol.13(1), pp.29-U130
01/01/2012
DOI: 10.1038/ni.2171
PMCID: PMC3242890
PMID: 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.
Details
- Title: Subtitle
- The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation
- Creators
- Anke Di - University of Illinois ChicagoXiao-Pei Gao - University of Illinois ChicagoFeng Qian - University of Illinois Urbana-ChampaignTakeshi Kawamura - University of Illinois Urbana-ChampaignJin Han - University of Illinois Urbana-ChampaignClaudie Hecquet - University of Illinois Urbana-ChampaignRichard D. Ye - University of Illinois Urbana-ChampaignStephen M. Vogel - University of Illinois ChicagoAsrar B. Malik - University of Illinois Chicago
- Resource Type
- Journal article
- Publication Details
- Nature immunology, Vol.13(1), pp.29-U130
- DOI
- 10.1038/ni.2171
- PMID
- 22101731
- PMCID
- PMC3242890
- NLM abbreviation
- Nat Immunol
- ISSN
- 1529-2908
- eISSN
- 1529-2916
- Publisher
- Springer Nature
- Number of pages
- 7
- Grant note
- Francis Families Foundation P01HL060678 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P01 HL77806 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2012
- Academic Unit
- Anesthesia
- Record Identifier
- 9985015819302771
Metrics
9 Record Views