IMMUNOLOGICAL RESEARCH ON THE PATHOGENESIS OF PREECLAMPSIA AND THE PREDICTION OF ITS MANIFESTATION.

先兆子痫发病机制及其表现预测的免疫学研究。

• 批准号: 10671516
• 负责人: FUJII Tomoyuki
• 金额: $ 2.11万
• 依托单位: UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671516/
• 关键词: CYTOKINE; HERBAL MEDICINE; HUMANLEUKOCYTE ANTIGEN-G; IMMUNOLOGY; NATURAL KILLER RECEPTOR; PLACENTA; PREECLAMPSIA; RECURRENT ABORTION; HLA-G; Th1サイトカイン; Th2サイトカイン; IL-2; ELISA

We have investigated the relationship between the pathogenesis of preeclampsia and human leukocyte antigen (HLA)-G which is thought to play an important role in maintaining pregnancy. First, we have established and enzyme-linked immunosorbent assay (ELISA) system to measure soluble HLA-G protein (Ref 1). Secondly, in regard to the fact that the expression of HLA-G on trophoblasts is attenuated and interleukin (IL)-2 is aberrantly expressed in decidual tissue in preeclamtic placenta, we analyzed the growth of HLA-G-negative and -positive trophoblast cell line in the culture with or without IL-2 supplementation. We found that the expression of HLA-G on trophoblastic cell line completely eliminated the growth-inhibitory effect of IL-2, which might be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia (Ref 2). Thirdly, we found that upon the contact with HLA-G, the amounts of T helper 1 (Th1) cytokines released from decidual mono … More nuclear cells and peripheral blood monon clear cells (PBMCs) were decreased, while the amounts of T helper 2 (Th2) cytokine from PBMCs was increased with Th2 cytokine release from decidual mononuclear cells being unchanged (Ref 3).We then investigated the pathogenesis of recurrent abortion and the mechanism of its immunotherapy using paternal mononuclear cells because as well as preeclampsia, the derangement of feto-maternal immune reaction is thought to play an important role in the pathogenesis of recurrent abortion. First, we found that HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of recurrent abortion (Ref 4). Secondly, the immunotherapy for recurrent aborters did not affect the expression of natural killer (NK) receptors regardless of the outcome of subsequent pregnancies, suggesting that recurrent aborters may benefit from the immunotherapy through mechanisms unrelated to alteration in NK receptor status (Ref 5). Thirdly, to gent insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate Th1 and Th2 cytokine release from PBMCs. Toki and Sai increased the release of Th1 cytokines, which may have therapeutic potential particularly in autoimmunity -related recurrent abortion where Th2 response is pathologically enhanced (Ref 6,7). Less

人类白细胞抗原（HLA）-G被认为在维持妊娠中起重要作用，我们研究了子痫前期发病机制与HLA-G的关系。首先，我们建立了酶联免疫吸附试验（ELISA）系统来测定可溶性HLA-G蛋白（参考文献1）。其次，针对子痫前期胎盘滋养层细胞HLA-G表达减弱，蜕膜组织中IL-2表达异常的事实，我们分析了HLA-G阴性和阳性滋养层细胞系在添加或不添加IL-2的培养中的生长情况。我们发现滋养层细胞系上HLA-G的表达完全消除了IL-2的生长抑制作用，这可能与妊娠期间母体对胎儿的耐受性及其紊乱有关，如先兆子痫（参考文献2）。第三，我们发现，在与HLA-G接触时，蜕膜单核细胞释放的T辅助细胞1（Th1）细胞因子的量， ...更多信息 核细胞和外周血莫农透明细胞（PBMCs）减少，而来自PBMCs的辅助性T细胞2（Th2）细胞因子的量增加，而来自蜕膜单核细胞的Th2细胞因子释放不变（参考文献3）。母-胎免疫反应紊乱在复发性流产的发病机制中起重要作用。首先，我们发现HLA-G等位基因异常在复发性流产的发病机制中几乎没有影响（参考文献4）。其次，无论后续妊娠的结果如何，复发性流产者的免疫治疗均不影响自然杀伤（NK）受体的表达，这表明复发性流产者可能通过与NK受体状态改变无关的机制从免疫治疗中获益（参考文献5）。第三，为了深入了解草药治疗复发性流产的经验性使用的基础，我们研究了Tokishakuyaku-san（Toki）和Sairei-to（Sai）是否调节PBMC中Th1和Th2细胞因子的释放。Toki和Sai增加了Th1细胞因子的释放，这可能具有治疗潜力，特别是在Th2应答病理性增强的自身免疫相关复发性流产中（参考文献6，7）。少

项目成果

Hyodo H, Fujii T, et al.: "Polymorphisms of RhD^<Va> and a new RhD^<Va>-like variant found in Japanese"Vox Sanguimis. (in press). (2000)

Hyodo H、Fujii T 等人：“RhD^<Va> 的多态性和日本人中发现的新的 RhD^<Va> 样变体”Vox Sanguimis。

Hanai Y, Fujii T, Kozuma S他: "Quantitative assessment of human leukocyte antigen-G protein in anniotic fiaid by a double determinant ELISA using anti-human leukocyte antroen-G specific antibody '87G'."American Journol of Reproductive Immunology. 41. 293-2

Hanai Y、Fujii T、Kozuma S 等人：“使用抗人白细胞 antroen-G 特异性抗体‘87G’，通过双决定簇 ELISA 对羊膜中的人白细胞抗原 G 蛋白进行定量评估。”美国生殖杂志免疫学41.293-2

Hamai Y, Fujii T, Yamashita T,Miki A, Hyodo H, Kozuma S, Geraghty DE, Taketani Y: "The expression of human leukocyte antigen-G on trophoblasts abolishes the growth-suppressing effect of interleukin-2 toward them."Am J Reprod Immunol. 41. 153-158 (1999)

Hamai Y、Fujii T、Yamashita T、Miki A、Hyodo H、Kozuma S、Geraghty DE、Taketani Y：“滋养层细胞上人类白细胞抗原 G 的表达消除了白细胞介素 2 对滋养层细胞的生长抑制作用。”Am

Fujii T, Kanai T, Kozuma S, Hamai Y, Hyodo H, Yamashita T, Miki A, Unno N, Taketani Y: "Theoretical basis for herbal medicines, Tokishakuyaku-san and Sairei-to, in the treatment of autoimmunity-related recurrent abortion by correcting T helper-1/T helper-

Fujii T、Kanai T、Kozuma S、Hamai Y、Hyodo H、Yamashita T、Miki A、Unno N、Taketani Y：“草药、Tokishakuyaku-san 和 Sairei-to 治疗自身免疫相关复发的理论基础