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.

本研究提出了一种基于上皮膜分子（例如转运蛋白）的细菌分泌的感测，从而导致肠道稳态的维持，这提出了一种新型的宿主微生物相互作用系统。这个新型系统主要介导宿主和概率之间的相互作用，包括杆菌和乳酸杆菌。相反，这项研究还表明，人类防御素（HD）5和6是从肠上皮分泌的代表性抗微生物肽，具有抗炎作用。此外，Isoleucine诱导HD-5分泌，这是一种氨基酸。本研究表明，这些有效的分子，包括细菌分泌，HDS和氨基酸（异亮氨酸），似乎是治疗肠道疾病的新型化合物。

项目成果

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

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.

Cytokine regulation of OCTN2 expression and activity in small and large intestine.

• DOI: 10.1002/ibd.21444
• 发表时间: 2011-04
• 期刊: INFLAMMATORY BOWEL DISEASES
• 影响因子: 4.9
• 作者: Fujiya, Mikihiro;Inaba, Yuhei;Musch, Mark W.;Hu, Shien;Kohgo, Yutaka;Chang, Eugene B.
• 通讯作者: Chang, Eugene B.

Lactobacillus Brevis SBC8803 Culture Supernatant Induces Cytoprotective Small Heat Shock Protein HSP27 in Human Intestinal Epithelial CaCo2/Bbe Cells by ctivating the p38 MAPK Pathway and Alleviates DSS-Induced Acute Colitis in C57BL/6 Mice.

短乳杆菌 SBC8803 培养上清液通过激活 p38 MAPK 途径诱导人肠上皮 CaCo2/Bbe 细胞中的细胞保护性小热休克蛋白 HSP27，并减轻 C57BL/6 小鼠中 DSS 诱导的急性结肠炎。

• 发表时间: 2010
• 作者: Segawa S;Fujiya M;Ueno N;Kobayashi N;Ito K;Kohgo Y.
• 通讯作者: Kohgo Y.

Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion.

变性的人α-防御素会减弱杀菌活性和抗酶消化的稳定性。

• 发表时间: 2007
• 期刊: Biochem Biophys Res Commun 358
• 作者: Cui H;Darmanin S;Natsuisaka M;Kondo T;Asaka M;Shindoh M;Higashino F;Hamuro J;Okada F;Kobayashi M;Nakagawa K;Koide H;Kobayashi M;Hiroki Tanabe
• 通讯作者: Hiroki Tanabe