Construction and delivery of gene therapy vector containing soluble TNFalpha receptor-IgGFc fusion gene for the treatment of allergic rhinitis.
Tumor necrosis factor alpha plays primary role in the pathogenesis of inflammatory diseases. TNFalpha is essential for antigen-specific IgE production and for the induction of Th2-type cytokines. The lack of TNFalpha inhibited the development of allergic rhinitis. In this study, the chimeric gene of soluble TNF receptor and IgGFc fragment (sTNFR-IgGFc) was cloned into the EBV-based plasmid pGEG. When the plasmid pGEG.sTNFR-IgGFc was transferred to endothelium cell, a considerable expression of the sTNFR-IgGFc fusion protein was detected. Moreover, the expression product in the supernatant could antagonize the cytolytic activity of TNFalpha on L929 cells. Then the plasmid was delivered into nasal mucosa of allergic rhinitis mice to determine its effect on this animal model. Results showed that symptoms in treated group were improved. Pathological examination showed the numbers of eosinophil, mast cell and IL-5(+) cells in treated groups were reduced compared with placebo group. These data showed that pGEG.sTNFR-IgGFc expression plasmid is potential for the treatment of allergic rhinitis, and suggest that the antagonist of TNFalpha may provide a new approach for the treatment of allergic rhinitis.
He
Jie
J
Institute for Viral Disease Control and Prevention, China CDC, Beijing 100052, China.
Wang
Tong
T
Yao
Lihong
L
Chen
Aijun
A
Zhou
Bing
B
Yu
Hong
H
Jia
Runqing
R
Cheng
Congsheng
C
Huan
Lifang
L
Zhang
Zhiqing
Z
D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000628:therapy*; D012220:Rhinitis / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha