title: Superoxide dismutase 3 limits collagen-induced arthritis in the absence of phagocyte oxidative burst.
abstract: Extracellular superoxide dismutase (SOD3), an enzyme mediating dismutation of superoxide into hydrogen peroxide, has been shown to reduce inflammation by inhibiting macrophage migration into injured tissues. In inflamed tissues, superoxide is produced by the phagocytic NOX2 complex, which consists of the catalytic subunit NOX2 and several regulatory subunits (e.g., NCF1). To analyze whether SOD3 can regulate inflammation in the absence of functional NOX2 complex, we injected an adenoviral vector overexpressing SOD3 directly into the arthritic paws of Ncf1(∗/∗) mice with collagen-induced arthritis. SOD3 reduced arthritis severity in both oxidative burst-deficient Ncf1(∗/∗) mice and also in wild-type mice. The NOX2 complex independent anti-inflammatory effect of SOD3 was further characterized in peritonitis, and SOD3 was found to reduce macrophage infiltration independently of NOX2 complex functionality. We conclude that the SOD3-mediated anti-inflammatory effect on arthritis and peritonitis operates independently of NOX2 complex derived oxidative burst.
authors.affiliation: Medicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Kelkka
authors.forename: Juha Petteri
authors.initials: JP
authors.lastname: Laurila
authors.forename: Outi
authors.initials: O
authors.lastname: Sareila
authors.forename: Peter
authors.initials: P
authors.lastname: Olofsson
authors.forename: Mikko Olavi
authors.initials: MO
authors.lastname: Laukkanen
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D019556:COS Cells; D008264:Macrophages / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010538:Peritonitis / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology*; D010587:Phagocytosis; D051381:Rats; D016897:Respiratory Burst; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases