The analysis of new physiological function of sphingolipid in the intestine

鞘脂在肠道中的新生理功能分析

• 批准号: 20688005
• 负责人: SATSU Hideo
• 金额: $ 16.64万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20688005/
• 关键词: 食品機能; 腸管上皮細胞; スフィンゴシン1リン酸; S1P受容体; Gタンパク質共役型受容体; サイトカイン; S1P2受容体; スフィンゴ脂質

We analyzed the physiological function of sphingosine-1-phoshate (S1P) and S1P receptors in the intestinal epithelial cells. It was observed that S1P_2 receptor is highly expressed in the intestinal epithelial cells (IECs). Then we analyzed the effect of S1P on immune function of IECs. Treatment of mouse IEC line with S1P additionally up-regulated the mRNA expression and secretion of IL-6 induced by Pam3CSK4 (TLR1/2 ligand) and also TLR2, 5, 7 ligands. S1P and S1P_2 agonist induced the IL-6 secretion and mRNA expression in the Pam3CSK4-treated IEC line and this effect was completely abolished by treatment with S1P_2 antagonist (JTE013). Luciferase reporter assay indicated that treatment with Pam3CSK4 induced the promoter activity of the murine IL-6 gene (from -375 to +15), and additional treatment with S1P_2 agonist further induced the IL-6 promoter activity. cAMP responsive element (CRE : from -183 to -175) on the murine IL-6 promoter was necessary for the induction by S1P_2 agonist. The siRNA targeting GNAS and PKA inhibitor (H-89) abolished the enhancement of IL-6 secretion by S1P and S1P_2 agonist in the Pam3CSK4-treated IECs. The expression level of IL-6 mRNA in the mouse ileum induced by Pam3CSK4 was significantly blocked by treatment with JTE013. These results suggest that S1P regulates cytokine production, especially IL-6, in IECs via S1P_2 and cAMP signaling pathway.

我们分析了肠上皮细胞中1-磷酸鞘氨醇（S1 P）及其受体的生理功能。结果表明，S1P_2受体在肠上皮细胞中有高表达。然后分析S1 P对IEC免疫功能的影响。用S1 P处理小鼠IEC系另外上调由Pam 3CSK 4（TLR 1/2配体）以及TLR 2、5、7配体诱导的IL-6的mRNA表达和分泌。S1 P和S1P_2激动剂诱导Pam 3CSK 4处理的IEC细胞分泌IL-6和mRNA表达，这种作用可被S1P_2拮抗剂（JTE 013）完全阻断。荧光素酶报告基因分析表明，Pam 3CSK 4诱导小鼠IL-6基因启动子活性（从-375到+15），S1 P2激动剂进一步诱导IL-6基因启动子活性。小鼠IL-6启动子上的cAMP反应元件（CRE：-183 ~-175）是S1P_2激动剂诱导IL-6表达所必需的。靶向GNAS和PKA抑制剂（H-89）的siRNA阻断了S1 P和S1P_2激动剂对Pam 3CSK 4处理的IEC分泌IL-6的促进作用。JTE 013处理可显著阻断Pam 3CSK 4诱导的小鼠回肠中IL-6 mRNA的表达水平。提示S1 P通过S1P_2和cAMP信号通路调节IEC细胞因子的产生，尤其是IL-6的产生。

项目成果

Synergistic effect of tumor necrosis factor-alpha and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells.

肿瘤坏死因子-α 和过氧化氢对诱导人肠 Caco-2 细胞产生 IL-8 的协同作用。

• 期刊: Inflammation in press
• 作者: Shin;H.S.;Zhao;Z.;Satsu;H.;Totsuka;M.;Shimizu;M.
• 通讯作者: M.

腸管上皮細胞においてTLRリガンドで誘導されるサイトカイン産生に対するスフィンゴシン-1-リン酸の作用とその機構解析

1-磷酸鞘氨醇对TLR配体诱导肠上皮细胞细胞因子产生的影响及其机制分析

• 发表时间: 2010
• 作者: 岩本拓;戸塚護;清水誠;薩秀夫
• 通讯作者: 薩秀夫

「機能性食品成分とトランスポーター」in「栄養・食品機能とトランスポーター」(竹谷豊、薩秀夫、伊藤美紀子、武田英二責任編集、日本栄養・食糧学会監修)

《营养/食品功能与转运蛋白》中的《功能性食品成分与转运蛋白》（竹谷丰、萨摩英夫、伊藤美纪子、武田英二主编，日本营养食品学会监修）

• 发表时间: 2011
• 作者: Yamada;S.;食の検定協会編;遠藤いず貴・大澤裕樹・丹下健;薩秀夫;大門高明;中曽根勝重;中原健二;薩秀夫
• 通讯作者: 薩秀夫

ヒト腸管上皮細胞を用いた食品機能・安全性評価

利用人肠上皮细胞评价食品功能和安全性

• 发表时间: 2010
• 期刊: BIOINDUSTRY,シーエムシー出版 27(7)(依頼総説)
• 作者: 薩秀夫;清水誠
• 通讯作者: 清水誠

Cycloheximide treatment induces the uptake of neutral and dibasic amino acids via activation of system b^<0,+> in human intestinal Caco-2 cells.

放线菌酮处理通过激活人肠道 Caco-2 细胞中的 b^<0,> 系统来诱导中性和二元氨基酸的摄取。

• 发表时间: 2009
• 期刊: J.Nutr.Sci.Vitaminol. 55
• 作者: Satsu;H.;Hyun;JS;Shin;HS;Shimizu;M.
• 通讯作者: M.