Construction and delivery of gene therapy vector containing soluble TNFα receptor-IgGFc fusion gene for the treatment of allergic rhinitis
Construction and delivery of gene therapy vector containing soluble TNFα receptor-IgGFc fusion gene for the treatment of allergic rhinitis
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DOI：
10.1016/j.cyto.2007.02.010
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发表时间：
2006-12-01
期刊：
影响因子：
3.8
通讯作者：
Zhang, Zhiqing
中科院分区：
文献类型：
--
作者：
He, Jie;Wang, Tong;Zhang, Zhiqing
肿瘤坏死因子a在炎症性疾病的发病机制中起主要作用。TNF α对于抗原特异性IgE产生和诱导Th 2型细胞因子是必需的。TNF α的缺乏抑制了过敏性鼻炎的发展。本研究将可溶性TNF受体与IgGFc片段的嵌合基因（sTNFR-IgGFc）克隆到EB病毒载体pGEG中。将pGEG-sTNFR-IgGFc质粒转染内皮细胞后，sTNFR-IgGFc融合蛋白在内皮细胞中有较高的表达。表达产物能拮抗TNF α对L929细胞的杀伤作用。将质粒导入变应性鼻炎小鼠鼻粘膜，观察其对变应性鼻炎模型的影响。结果显示治疗组症状改善明显。病理学检查显示治疗组嗜酸性粒细胞、肥大细胞和IL-5阳性细胞数量较安慰剂组减少。这些结果表明，pGEG-sTNFR-IgGFc表达质粒具有治疗变应性鼻炎的潜力，提示TNF α拮抗剂可能为变应性鼻炎的治疗提供新的途径。(c)2007爱思唯尔有限公司保留所有权利。
Tumor necrosis factor a plays primary role in the pathogenesis of inflammatory diseases. TNFot is essential for antigen-specific IgE production and for the induction of Th2-type cytokines. The lack of TNF alpha 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 TNFot 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 TNFa may provide a new approach for the treatment of allergic rhinitis. (c) 2007 Elsevier Ltd. All rights reserved.