Generation of a sensitive TNFR2-specific murine assays system
Generation of a sensitive TNFR2-specific murine assays system
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DOI：
10.1691/ph.2016.5183
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发表时间：
2016-05-01
期刊：
影响因子：
1.6
通讯作者：
Tsunoda, S.
中科院分区：
文献类型：
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作者：
Ando, D.;Kamada, H.;Tsunoda, S.
肿瘤坏死因子（TNF）/TNF受体（TNFR 1/TNFR 2）被认为是治疗难治性疾病（包括自身免疫性疾病和恶性肿瘤）的潜在药物靶点。然而，它们的具体功能，特别是在TNFR 2的情况下，知之甚少。在这项研究中，我们构建了一个小鼠TNFR 2（mTNFR 2）介导的生物测定系统，显示没有小鼠TNFR 1（mTNFR 1）的影响，以筛选mTNFR 2-选择性刺激剂。用编码mTNFR 2/小鼠Fas（mFas）嵌合受体的基因转染小鼠TNFR 1（-/-）R2（-/-）前脂肪细胞，其中mTNFR 2的细胞外和跨膜结构域与mFas的细胞内结构域融合。我们的结果表明，该细胞系表现出高度敏感的mTNFR 2介导的细胞毒性作用。我们建议，这种mTNFR 2介导的生物测定系统将是一个有用的工具，筛选mTNFR 2选择性刺激剂。
Tumor necrosis factor (TNF)/TNF receptors (TNFR1/TNFR2) are considered to be potential drug targets to treat refractory diseases, including autoimmune diseases and malignant tumors. However, their specific functions, especially in the case of TNFR2, are poorly understood. In this study, we constructed a mouse TNFR2 (mTNFR2)-mediated biological assay system that shows no effects of mouse TNFR1 (mTNFR1) in order to screen mTNFR2-selective stimulating agents. Mouse TNFR1(-/-)R2(-/-) preadipocytes were transfected with the gene encoding the mTNFR2/mouse Fas (mFas) chimeric receptor in which the extracellular and transmembrane domains of mTNFR2 were fused to the intracellular domain of mFas. Our results demonstrated that this cell line exhibits highly sensitive mTNFR2-mediated cytotoxic effects. We propose that this mTNFR2-mediated biological assay system would be a useful tool to screen for mTNFR2-selective stimulating agents.