NADPH oxidase (NOX) isoforms together have multiple functions that are important for normal physiology and have been implicated in the pathogenesis of a broad range of diseases, including atherosclerosis, cancer and neurodegenerative diseases. The phagocyte NADPH oxidase (NOX2) is critical for antimicrobial host defence. Chronic granulomatous disease (CGD) is an inherited disorder of NOX2 characterized by severe life-threatening bacterial and fungal infections and by excessive inflammation, including Crohn's-like inflammatory bowel disease (IBD). NOX2 defends against microbes through the direct antimicrobial activity of reactive oxidants and through activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the breakdown of cell membranes and extracellular release of chromatin and neutrophil granular constituents that target extracellular pathogens. Although the immediate effects of oxidant generation and NETosis are predicted to be injurious, NOX2, in several contexts, limits inflammation and injury by modulation of key signalling pathways that affect neutrophil accumulation and clearance. NOX2 also plays a role in antigen presentation and regulation of adaptive immunity. Specific NOX2-activated pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor that induces antioxidative and cytoprotective responses, may be important therapeutic targets for CGD and, more broadly, diseases associated with excessive inflammation and injury.
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Review Article| February 17 2016
NOX2-dependent regulation of inflammation
Kelly L. Singel;
Brahm H. Segal
*Departments of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, U.S.A.
†Departments of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, U.S.A.
‡Department of Medicine, University at Buffalo School of Medicine, Buffalo, NY 14214, U.S.A.
Correspondence: Brahm H. Segal (email email@example.com).
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Publisher: Portland Press Ltd
Received: September 17 2015
Revision Received: November 25 2015
Accepted: December 18 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
Kelly L. Singel, Brahm H. Segal; NOX2-dependent regulation of inflammation. Clin Sci (Lond) 1 April 2016; 130 (7): 479–490. doi: https://doi.org/10.1042/CS20150660
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