Expression of sTNFR-IgGFc fusion gene in endothelial cell and its application in gene therapy for rheumatoid arthritis.
- Author:
Jie HE
1
;
Li-Hong YAO
;
Ai-Jun CHEN
;
Hong YU
;
Run-Qing JIA
;
Cong-Sheng CHENG
;
Li-Fang HUAN
;
Zhi-Qing ZHANG
Author Information
1. Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Arthritis, Rheumatoid;
chemically induced;
therapy;
Collagen Type II;
Endothelial Cells;
metabolism;
Escherichia coli;
genetics;
metabolism;
Etanercept;
Genetic Therapy;
Humans;
Immunoglobulin G;
biosynthesis;
genetics;
therapeutic use;
Male;
Mice;
Mice, Inbred DBA;
Receptors, Tumor Necrosis Factor;
biosynthesis;
genetics;
therapeutic use;
Recombinant Fusion Proteins;
biosynthesis;
genetics;
therapeutic use;
Transfection;
Tumor Necrosis Factor-alpha;
metabolism
- From:
Chinese Journal of Biotechnology
2006;22(3):378-383
- CountryChina
- Language:Chinese
-
Abstract:
Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine, acting as a regulator of inflammation and immunity. TNFalpha plays a critical role in the pathogenesis of rheumatoid arthritis. Blocking of TNFa activity suppressed inflammatory tissue damage. In present study, the chimeric gene of soluble TNF receptor and IgG Fc fragment (sTNFR-IgG FC) was cloned into the mammalian cell expression vector pStar. When the plamid pStar/sTNFR-IgGFc-GFP was transfected into endothelial cells, a considerable expression of the sTNFR-IgG Fc fusion protein was detected. Moreover, the product in 100microL expression supernatant could completely antagonize the cytolytic effect of 1ng TNFa on L929 cells, even at 1/64 dilution. Then the plasmid was delivered into CIA-induced rheumatoid arthritis mice by tail vein injection. The expression of sTNFR-IgG Fc was detected in liver by RT-PCR. Animals in treatment group showed reduced symptoms of arthritis and more active. This treatment induced decrease of synovial incrassation and prevented the cartilage destruction of the mice RA model. These results show that tail vein injection is an effective way for gene therapy and sTNFR-IgGFc expression plasmid is potential for the treatment of rheumatoid arthritis.
