Establishment for an effective medical treatment on the basis of the physiological activities of functional mediators involved in the regulation of immunological systems

基于参与免疫系统调节的功能介质的生理活性建立有效的医疗方法

• 批准号: 10670424
• 负责人: OHTSUKI Kenzo
• 金额: $ 2.05万
• 依托单位: Kitasato University
• 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 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670424/
• 关键词: Anti-inflammation; Signal mediator; Immunological mediator; Protein kinase; Phosphorylation; Transcriptional factor; Diagnosis; Polyphenol antioxidant compound; 抗炎症剤; HIV-1遺伝子産物; 抗ウイルス作用; Protein kinaseによるリン酸化; 抗炎症作用; プロテインキナーゼ; グリチルリチン; シグ

1. To isolate and identify functional mediators involved in immunological responses, a glycyrrhizin (GL)-affinity column was prepared. Using the GL-affinity column, several GL-binding proteins (gbPs), such as arachidonic acid cascade related enzymes, signal and immunological regulatory factors, were selectively purified from various tissues and rhematoid synovial fluids.2. To characterize potent CK-II inhibitors isolated from medical plants Ed Chinese medicines, the inhibitory effects of these compounds on the CK-II-mediated phosphorylation of functional mediators and viral gene products (HIV-1 RT and PR) were determined in vitro It was found that a glycyrrhetinic acid derivative (oGA) and polyphenol-containing antioxidant compounds (catechin, qercetin and EGCG) function as effective CK-II inhibitors.3. To establish the assay system for evaluation of potent CK-II inhibitors isolated from Chinese medicines and medical plants, the inhibitory effects of the CK-II inhibitors on the physiological activities of the gbPs were determined in vitro. The sensitive assay systems for p96 (lipoxygenase), p54 (hyaluronidase), 31 (HMG-1) and p14 (sLPA2-IIA) in sera of patients had established as useful for clinical diagnosis of microbial inflammation and allergic diseases.

1. 为了分离和鉴定参与免疫反应的功能介质，制备了甘草甜素（GL）亲和柱。利用GL亲和柱，从多种组织和类风湿滑液中选择性纯化了多种GL结合蛋白(gbPs)，如花生四烯酸级联相关酶、信号和免疫调节因子。2．为了表征从药用植物和中药中分离出的有效 CK-II 抑制剂，在体外测定了这些化合物对 CK-II 介导的功能介质和病毒基因产物（HIV-1 RT 和 PR）磷酸化的抑制作用。发现甘草次酸衍生物（oGA）和含多酚的抗氧化化合物（儿茶素、槲皮素和EGCG）可作为有效的CK-II抑制剂。3．为了建立从中药和药用植物中分离的强效CK-II抑制剂的测定体系，体外测定CK-II抑制剂对gbPs生理活性的抑制作用。患者血清中 p96（脂氧合酶）、p54（透明质酸酶）、31（HMG-1）和 p14（sLPA2-IIA）的灵敏检测系统已被证实可用于微生物炎症和过敏性疾病的临床诊断。

项目成果

Ohtsuki, K., Maekawa, T., Harada, S., Karino, A., Morikawa, Y. end Ito, M.: "Biochemical characterization of HIV-1Rev as a potent activator of casein kinase II in vitro"FEBS Letters. 428. 235-240 (1998)

Ohtsuki, K.、Maekawa, T.、Harada, S.、Karino, A.、Morikawa, Y. 和 Ito, M.：“HIV-1Rev 作为酪蛋白激酶 II 体外有效激活剂的生化特征”FEBS Letters

Ohtsuki, K.: "Anti-HIV-1 mechanism of glycyrrhizin"Minopha. Med. Rev.. 45. 1-14 (2000)

Ohtsuki, K.：“甘草甜素的抗 HIV-1 机制”Minopha。

Karino, A., Okano, M., Hatomi, M., Nakamura, T. and Ohtsuki, K.: "Biochemical Characterization of a CK-I-like actin kinase responsible for the actin-induced suppression of CK-II activity in vitro"Biochim. Biophys. Acta. 1472. 603-616 (1999)

Karino, A.、Okano, M.、Hatomi, M.、Nakamura, T. 和 Ohtsuki, K.：“CK-I 样肌动蛋白激酶的生化特征，该激酶负责肌动蛋白诱导的 CK-II 活性抑制

Abe,Y.et al.: "Characterization of an Apoptosis-induced factor in Habu snake venom as a glycyrrhizin (GL)-binding protein potently inhibited by GL in vitro" Biol.Pharm.Bull.21・9. 924-927 (1998)

Abe, Y. 等人：“Habu 蛇毒中凋亡诱导因子作为甘草酸 (GL) 结合蛋白的特征，在体外受 GL 有效抑制”Biol.Pharm.Bull.21·927（ 1998）

Abe, Y., Shimoyma, S, Munakata, H., Ito, J, Nagata, N., and Ohtsuki, K.: "Characterization of an apoptosis-inducing factor in Habu snake venom as a glyrrhizin (GL)-binding protein potently inhibited by GL in vitro"Biol. Pharm. Bull. 21(9). 924-927 (1998)

Abe, Y.、Shimoyma, S、Munakata, H.、Ito, J、Nagata, N. 和 Ohtsuki, K.：“Habu 蛇毒中凋亡诱导因子作为甘草酸 (GL) 结合蛋白的表征