Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst

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 o...

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Main Authors: Tiina Kelkka, Juha Petteri Laurila, Outi Sareila, Peter Olofsson, Mikko Olavi Laukkanen, Rikard Holmdahl
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/730469
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author Tiina Kelkka
Juha Petteri Laurila
Outi Sareila
Peter Olofsson
Mikko Olavi Laukkanen
Rikard Holmdahl
author_facet Tiina Kelkka
Juha Petteri Laurila
Outi Sareila
Peter Olofsson
Mikko Olavi Laukkanen
Rikard Holmdahl
author_sort Tiina Kelkka
collection DOAJ
description 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.
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publishDate 2012-01-01
publisher Wiley
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series Mediators of Inflammation
spelling doaj-art-930f0fcd70da4dd889a2e2e74d5086652025-02-03T05:51:26ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/730469730469Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative BurstTiina Kelkka0Juha Petteri Laurila1Outi Sareila2Peter Olofsson3Mikko Olavi Laukkanen4Rikard Holmdahl5Medicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMedicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMedicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandRedoxis AB, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46 Göteborg, SwedenMedicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandMedicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, FinlandExtracellular 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.http://dx.doi.org/10.1155/2012/730469
spellingShingle Tiina Kelkka
Juha Petteri Laurila
Outi Sareila
Peter Olofsson
Mikko Olavi Laukkanen
Rikard Holmdahl
Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
Mediators of Inflammation
title Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
title_full Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
title_fullStr Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
title_full_unstemmed Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
title_short Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst
title_sort superoxide dismutase 3 limits collagen induced arthritis in the absence of phagocyte oxidative burst
url http://dx.doi.org/10.1155/2012/730469
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