STUDY ON THE IMMUNOMODURATORY ACTION OF BILE ACIDS

胆汁酸的免疫调节作用的研究

• 批准号: 06454254
• 负责人: MAKINO Isao
• 金额: $ 4.35万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454254/
• 关键词: bile acids; transcription factors; immunology; molecular biology; gastroenterology; MHC; 免疫応答; グルココルチコイド; T細胞; MHC class I; プロテインキナーゼC

The immunomodulatory action of bile acids was studied with special reference to1) regulation of MHC class I & II gene expression,2) interplay between the glucocorticoid receptor and bile acids,3) effects of bile acids on T cell signaling.1) Bile acids were shown to upregulate gene expression of MHC class I,the mechanism for which is suggested to be activation of protein kinase C.Currently, isoform analysis of bile acidrelated protein kinase C is ongoing. Concerning MHC class II gene expression, bile acid ursodeoxycholic acid represses upregulatory effect of IFN-gamma, and this repression is shown to be mediated ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid.2) bile acid ursodeoxycholic acid is shown to activated cytosolic latent glucocorticoid receptor into functional species in the absence of ligands. The molecular mechanism is unknown.3) Already we have obtained preliminary data suggesting influence of bile acids on the intracellular signaling events in antigen-activated T cells.

研究了胆汁酸的免疫调节作用，特别是1）调节MHC I类和II类基因表达，2）糖皮质激素受体和胆汁酸之间的相互作用，3）胆汁酸对T细胞信号传导的影响。1）胆汁酸显示上调MHC I类基因表达，其机制被认为是激活蛋白激酶C。目前，胆汁酸相关蛋白激酶C的亚型分析正在进行中。关于MHC II类基因的表达，胆汁酸熊去氧胆酸抑制IFN-γ的上调作用，并且这种抑制被证明是由熊去氧胆酸介导的糖皮质激素受体的配体非依赖性激活。2）胆汁酸熊去氧胆酸被证明在配体缺乏的情况下激活胞浆潜伏的糖皮质激素受体成为功能性物种。分子机制尚不清楚。3）我们已经获得了初步数据，表明胆汁酸对抗原激活的T细胞中的细胞内信号事件的影响。

项目成果

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Hirano F 等人：“培养的人肝癌细胞中胆汁酸对 MHC I 类 mRNA 表达的调节”Biochem。

Hirotoshi Tanaka, Yuichi Makino, Karin-Dahlman Wright, Jan-Ake Gustafsson, Kensaku Okamoto, Isao Makino: "Zinc ions antagonize the inhibitory effect of aurothiomalate on glucocorticoid receptor function at physiological concentrations." Mol.Pharmacol. 48.

Hirotoshi Tanaka、Yuichi Makino、Karin-Dahlman Wright、Jan-Ake Gustafsson、Kensaku Okamoto、Isao Makino：“锌离子在生理浓度下拮抗金硫苹果酸盐对糖皮质激素受体功能的抑制作用。”

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Fuminori Hirano, Hirotoshi Tanaka, Yuichi Makino, Kensaku Okamoto, Masaki Hiramoto, Hiroshi Handa, Isao Makino.: "Induction of the transcription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids." Carcinogenesis. (i

Fuminori Hirano、Hirotoshi Tanaka、Yuichi Makino、Kensaku Okamoto、Masaki Hiramoto、Hiroshi Handa、Isao Makino.：“暴露于胆汁酸后培养的人结肠腺癌细胞中转录因子 AP-1 的诱导”。