The therapeutic effect of extracellular superoxide dismutase (EC-SOD) mouse embryonic fibroblast (MEF) on collagen-induced arthritis (CIA) mice.
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.
Yu
Dong Hoon
DH
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea.
Kim
Myoung Ok
MO
Kim
Sung Hyun
SH
Shin
Mi Jung
MJ
Kim
Bong Soo
BS
Kim
Hei Jung
HJ
Lee
Sang Ryeul
SR
Lee
Sang Gyu
SG
Yoo
Seung-Ah
SA
Kim
Wan Uk
WU
Hyun
Byung Hwa
BH
Park
Young Sik
YS
Kim
Tae Yoon
TY
Ryoo
Zae Young
ZY
D000818:Animals; D001169:Arthritis, Experimental / Q000601:surgery*; D017690:Cell Transplantation / Q000379:methods*; D005347:Fibroblasts / Q000201:enzymology / Q000637:transplantation*; D006801:Humans; D053547:Keratin-14 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
C507540:KRT14 protein, human; D053547:Keratin-14; D013482:Superoxide Dismutase