Development of a novel treatment for inflammatory bowel disease via the regulation of the bacteria recognition system and effective molecules derived from bacteria

通过调节细菌识别系统和细菌衍生的有效分子开发炎症性肠病的新型治疗方法

• 批准号: 19390194
• 负责人: KOHGO Yutaka
• 金额: $ 10.07万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390194/
• 关键词: 消化器学(食道,胃,小腸,大腸); 炎症性腸疾; 自然免疫; Human defensin; Competence and sporulation factor; OCTN; バシラス菌; 乳酸菌; Bacillus subtilis; 炎症性腸疾患

The present study proposed a novel system of host-microbial interactions based on the sensing of bacterial secretions by epithelial membrane molecules such as transporters, leading to the maintenance of intestinal homeostasis. This novel system mainly mediates the interaction between the host and probitoics, including bacilli and lactobacilli. Conversely, this study also showed that human defensin (HD) 5 and 6, which are representative anti-microbial peptides secreted from the intestinal epithelia, possess an anti-inflammatory effect. Furthermore, HD-5 secretion was induced by isoleucine, which is an amino acid. The present study indicated that these effective molecules, including bacterial secretions, and HDs, and an amino acid (isoleucine), appear to be a novel potential compound for the treatment of intestinal disorders.

本研究提出了一种新的宿主-微生物相互作用系统，该系统基于上皮膜分子（例如转运蛋白）对细菌分泌物的感知，从而维持肠道稳态。这个新系统主要介导宿主和益生菌（包括杆菌和乳酸杆菌）之间的相互作用。相反，这项研究还表明，人类防御素（HD）5和6是肠上皮细胞分泌的代表性抗菌肽，具有抗炎作用。此外，HD-5的分泌是由氨基酸异亮氨酸诱导的。目前的研究表明，这些有效分子，包括细菌分泌物、HD 和氨基酸（异亮氨酸），似乎是治疗肠道疾病的新型潜在化合物。

项目成果

Heat-killed Lactobaccilus brevis SBC8803 improves intestinal injury in a murine model of colitis by protecting the intestinal epithelia and regulating pro-inflammatory cytokines.

热灭活短乳杆菌 SBC8803 通过保护肠上皮和调节促炎细胞因子来改善小鼠结肠炎模型中的肠道损伤。

• 发表时间: 2010
• 作者: Ueno N;Fujiya M;Kohgo Y.
• 通讯作者: Kohgo Y.

Heat killed Lactobaccilus brevis SBC8803 improves intestinal injury in a murine model of colitis via the enhancement of the intestinal barrier function and the down-regulation of pro-inflammatory cytokines.

热灭活短乳杆菌 SBC8803 通过增强肠道屏障功能和下调促炎细胞因子来改善小鼠结肠炎模型中的肠道损伤。

• 发表时间: 2010
• 作者: Fujiya M;Ueno N;Segawa S;Nata T;Moriichi K;Tanabe H;Mizukami Y;Kobayashi N;Ito K;Kohgo Y
• 通讯作者: Kohgo Y

Infliximab may prevent post-operative recurrences in Crohn's disease.

英夫利昔单抗可以预防克罗恩病术后复发。

• 发表时间: 2009
• 作者: K.Okamoto;T.Ashida;R.Sugiyama;T.Nata;Y.Nomura;N.Ueno;C.Ishikawa;Y.Inaba;T.Ito;K.Moriihi;H.Tanabe;M.Fujiya;Y.Kohgo
• 通讯作者: Y.Kohgo

The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal Homeostasis via OCTN2, a host cell membrane transporter

• DOI: 10.1016/j.chom.2007.05.004
• 发表时间: 2007-06-01
• 期刊: CELL HOST & MICROBE
• 影响因子: 30.3
• 作者: Fujiya, Mikihiro;Musch, Mark W.;Chang, Eugene B.
• 通讯作者: Chang, Eugene B.

Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo

• DOI: 10.1159/000242114
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF INNATE IMMUNITY
• 影响因子: 5.3
• 作者: Ishikawa, Chisato;Tanabe, Hiroki;Kohgo, Yutaka
• 通讯作者: Kohgo, Yutaka