[Expression of sTNFR-IgGFc fusion gene in endothelial cell and its application in gene therapy for rheumatoid arthritis].
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.
He
Jie
J
Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
Yao
Li-Hong
LH
Chen
Ai-Jun
AJ
Yu
Hong
H
Jia
Run-Qing
RQ
Cheng
Cong-Sheng
CS
Huan
Li-Fang
LF
Zhang
Zhi-Qing
ZQ
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000628:therapy*; D024043:Collagen Type II; D042783:Endothelial Cells / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D000068800:Etanercept; D015316:Genetic Therapy; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D024043:Collagen Type II; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept