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Mediators of Inflammation
Volume 2012, Article ID 730469, 9 pages
http://dx.doi.org/10.1155/2012/730469
Research Article

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

1Medicity Research Laboratory, University of Turku, Tykistökatu 6 A, 20520 Turku, Finland
2Turku Doctoral Programme of Biomedical Sciences, Kiinamyllynkatu 13, 20520 Turku, Finland
3Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden
4Redoxis AB, Sahlgrenska Science Park, Medicinaregatan 8A, 413 46 Göteborg, Sweden
5Fondazione SDN, 80143 Naples, Italy

Received 14 September 2011; Revised 21 November 2011; Accepted 12 December 2011

Academic Editor: Christoph Aufricht

Copyright © 2012 Tiina Kelkka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.