The Therapeutic Effect of Extracellular Superoxide Dismutase (EC-SOD) Mouse Embryonic Fibroblast (MEF) on Collagen-Induced Arthritis (CIA) Mice

Abstract

Rheumatoid arthritis is a chronic inflammatory disease. The generation of reactive oxygen species (ROS) within an inflamed joint has been suggested as playing a significant pathogenic role. Extracellular superoxide dismutase (EC-SOD) is a major scavenger enzyme of ROS, which has received growing attention for its therapeutic potential. To investigate the therapeutic effect of EC-SOD in mice with collagen-induced arthritis (CIA), we used mouse embryonic fibroblast (MEF) of transgenic mice that overexpresses EC-SOD on the skin by using hK14 promoter. DBA/1 mice that had been treated with bovine type II collagen were administrated subcutaneous injections of EC-SOD transgenic MEF (each at 1.4 x 10(60 cells) on days 28, 35, and 42 after primary immunization. To test EC-SOD activity, blood samples were collected in each group on day 49. The EC-SOD activity was nearly 1.5-fold higher in the transgenic MEF-treated group than in the nontransgenic MEF-treated group (p < 0.05). The severity of arthritis in mice was scored in a double-blind manner, with each paw being assigned a separate clinical score. The severity of arthritis in EC-SOD transgenic MEF-treated mice was significantly suppressed in the arthritic clinical score (p < 0.05). To investigate the alteration of cytokine levels, ELISA was used to measure blood samples. Levels of IL-1beta and TNF-alpha were reduced in the transgenic MEF-treated group (p < 0.05). Abnormalities of the joints were examined by H&E staining. There were no signs of inflammation except for mild hyperplasia of the synovium in the transgenic MEF-treated group. The proliferation of CII-specific T cells was lower in the transgenic MEF-treated mice than in those in the other groups. The transfer of EC-SOD transgenic MEF has shown a therapeutic effect in CIA mice and this approach may be a safer and more effective form of therapy for rheumatoid arthritis.

The expression of mitochondrial, cytoplasmic and extracellular superoxide dismutase in the colonic wall of pigs suffering from swine dysenteria

“…It is believed to be involved in the cardiovascular disorders (Gongora et al 2006) and in lung diseases (Ganguly et al 2006). However, the involvement of SOD3 in the inflammation may be illustrated by the protective effect of SOD3 on the collagen-induced arthritis in mice (Yu et al 2008). The strong increase of SOD3 expression in the inflamed porcine colonic mucosa may suggest the protective process taking place in the dysenteric porcine colon.…”

Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis

“…Furthermore, engraftment of the EC-SOD transgenic mouse embryonic fibroblast repressed inflammatory cytokines and the CII-specific T cells (Yu et al, 2008). In this study, the transgenic mice over-expressed EC-SOD in joint tissue and this protein was located in the lining layer of the synovium and endotherial cells in the sub lining.…”

“…In the previous study, it has already been shown that the transfer of EC-SOD transgenic mouse embryonic fibroblast (MEF) represses the inflammatory arthritis (Yu et al, 2008). However, there is a question whether the over expression of EC-SOD on arthritic joint could also suppress the progression of disease or not.…”

Regulation of inflammatory responses and fibroblast‐like synoviocyte apoptosis by calcineurin‐binding protein 1 in mice with collagen‐induced arthritis

“…The most widely used pharmacologic inhibitors of calcineurin are cyclosporine and tacrolimus (48). Both drugs exhibit potent immunosuppressive activity and have been used in the treatment of many chronic inflammatory diseases, including RA (29). However, systemic administration of these drugs can produce significant side effects.…”

“…Age‐matched male DBA/1 mice (Charles River) and CABIN‐1–overexpressing mice were immunized with bovine type II collagen (CII; Chondrex) at 8–12 weeks of age, as previously described (29). Briefly, CII was dissolved at a concentration of 0.25% in 0.01 N acetic acid.…”