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.
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea.
Dong Hoon
DH
Yu
Myoung Ok
MO
Kim
Sung Hyun
SH
Kim
Mi Jung
MJ
Shin
Bong Soo
BS
Kim
Hei Jung
HJ
Kim
Sang Ryeul
SR
Lee
Sang Gyu
SG
Lee
Seung-Ah
SA
Yoo
Wan Uk
WU
Kim
Byung Hwa
BH
Hyun
Young Sik
YS
Park
Tae Yoon
TY
Kim
Zae Young
ZY
Ryoo
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