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Development of moleculartargeted therapy for EBV-infected NK cell lymphocytosis in the patients with hypersensitivity to mosquito bites

蚊虫叮咬过敏患者 EBV 感染 NK 细胞淋巴细胞增多的分子靶向治疗进展

基本信息

批准号：
18591257
负责人：
ASADA Hideo
金额：
$ 2.49万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591257/
关键词：
hypersensitivity to mosquito bites EB virus malignant lymphoma oncogene siRNA NK T cells

项目摘要

Hypersensitivity to mosquito bites (HMB) is characterized by intense local skin symptoms, which consist of not only erythema or bulla but also ulceration or scarring, and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. The patients with lymphoproliferation of EB virus (EBV) -infected NK/T cells, including NK/T cell leukemia/lymphoma, often show the clinical manifestation of HMB. We have demonstrated that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4^+ T cells, which may be involved in the proliferation of NK cells. The purpose of our present study is to design specific siRNA against LMP1, and transfer the siRNA into EBV-infected NK/T cells to investigate a function of LMP1 in EBV-infected NK/T cell proliferation. The goal of this study is to develop the molecular-targeted therapy for EBV-infected NK cell lymphocytosis in the patients with HMB. At first, we decided the optimum condition of siRNA transfection into lymphocytes using Oligofectamine. Next, we designed the candidates of LMP1-siRNA, and transfer them into EBV-infected NK/T cells. However, the inhibition effect of LMP1 mRNA expression by the LMP1-siRNA is poorly reproducible. After changing the transfection reagent to PrimaPort (CREDIA JAPAN), the transfection efficiency was improved, and the LMP1-siRNA significantly inhibited LMP1 mRNA expression, but did not suppress EBV-infected NK/T cell proliferation.

蚊虫叮咬过敏（HMB）的特点是局部皮肤症状强烈，不仅包括红斑或大疱，还包括溃疡或瘢痕，以及全身症状，如高烧、淋巴结病和肝脾肿大。EB病毒（EBV）感染NK/T细胞的淋巴增生患者，包括NK/T细胞白血病/淋巴瘤，临床常表现为HMB。我们已经证明蚊虫叮咬可以通过蚊子抗原特异性CD4^+ T细胞诱导NK细胞中病毒致癌基因LMP1的表达，这可能与NK细胞的增殖有关。本研究的目的是设计针对LMP1的特异性siRNA，并将siRNA转移到ebv感染的NK/T细胞中，以研究LMP1在ebv感染的NK/T细胞增殖中的功能。本研究的目的是开发ebv感染的HMB患者NK细胞淋巴细胞增多症的分子靶向治疗方法。首先，我们确定了用低聚咖啡胺转染siRNA进入淋巴细胞的最佳条件。接下来，我们设计了候选的LMP1-siRNA，并将其转移到ebv感染的NK/T细胞中。然而，LMP1- sirna对LMP1 mRNA表达的抑制作用可重复性较差。将转染试剂改为primapport （CREDIA JAPAN）后，转染效率提高，LMP1- sirna显著抑制LMP1 mRNA表达，但不抑制ebv感染的NK/T细胞增殖。