title: Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation.
abstract: The current review on the function of neutrophil cytosolic factor 1 (NCF1) and induced reactive oxygen species (ROS) is based on a genetic search for the major genes controlling autoimmune inflammatory disorders. Surprisingly, the disease-promoting allele determined a lower ROS response and was therefore in complete contrast to the prevailing dogma. Once cloned, it opened the possibility to dissect this complex field from a new angle and with the possibilities to study the role of ROS in vivo. We found that NCF1 and NADPH oxidase 2 (NOX2) complex-derived ROS is an important regulator of several chronic inflammatory disorders by using models for rheumatoid arthritis, multiple sclerosis, psoriasis and psoriasis arthritis, gout, and lupus. ROS could therefore affect many different types of diseases and the common denominator seems to be that ROS regulate macrophages, which prevents inflammation from going chronic. The role of ROS is currently changing from being seen as toxic agents that will promote inflammation toward a more complex view with ROS as crucial regulators of immune and inflammatory pathways.
authors.affiliation: Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.|Medicity Research Laboratory, University of Turku, Turku, Finland.|Medical Immunopharmacologic Research, Southern Medical University, Guangzhou, China.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.|Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Sareila
authors.affiliation: Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lina M
authors.initials: LM
authors.lastname: Olsson
authors.affiliation: Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Bäckdahl
authors.affiliation: Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: NOX2; Ncf1; autoimmunity; inflammation; reactive oxygen species