Prevention of colitic cancer by IL-6 trans-signaling inhibitors

IL-6 反式信号抑制剂预防结肠癌

• 批准号: 19590741
• 负责人: MITSUYAMA Keichi
• 金额: $ 2.5万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-19590741/
• 关键词: 炎症性腸疾患; colitic cancer; IL-6 trans-signaling; STAT3; 可溶性gp130-Fc; 可溶性gp 130-Fc; 可溶性gp130

Colitic cancer is a large bowel cancer that occurs in a long-standing inflammatory bowel disease. The role of the IL-6/STAT3 pathway in the development of colitic cancer has not been fully understood. This study was conducted to investigate whether IL-6 trans-signaling contributes to the development of colitic cancer. Chronic colitis was induced by dextran sodium sulfate (DSS) to BALB/c mice. Colitic cancer was induced by additional DSS treatment to colitis-affected mice. IL-6 expression increased in the colon of colitis- and colitic cancer-affected mice, and this expression was restricted to lamina propria-macrophages. Both IL-6R and TACE expressions increased in macrophages in colitis tissue, and soluble IL6R was increased in these tissues. In contrast, IL-6R generation was reduced in the colonic epithelial cells in colitis- and colitic cancer-mice and was associated with increased expression of gp130 and phospho-STAT3. It should be noted that pre-treatment of soluble gp130Fc significantly reduced the tumorigenesis in the colon. IL-6 trans-signaling in epithelial cells, induced by macrophage-derived IL-6/soluble IL-6R, plays a crucial role in the development of colitic cancer. Soluble gp130Fc may be effective for the prevention of colitic cancer.

结肠炎是一种发生在长期炎症性肠病中的大肠癌。IL-6/STAT3通路在结肠炎发展中的作用尚未完全清楚。本研究旨在探讨IL-6反式信号传导是否与大肠癌的发生有关。右旋糖酐硫酸钠（DSS）诱导BALB/c小鼠慢性结肠炎。对结肠炎小鼠进行DSS治疗，可诱导结肠炎癌变。IL-6在结肠炎和结肠炎小鼠的结肠中表达增加，并且这种表达仅限于固有层巨噬细胞。结肠炎组织巨噬细胞中IL-6R和TACE表达均升高，可溶性IL6R在结肠炎组织中升高。相比之下，结肠炎和结肠炎小鼠结肠上皮细胞中IL-6R的生成减少，并与gp130和phospho-STAT3的表达增加有关。值得注意的是，可溶性gp130Fc预处理显著降低了结肠肿瘤的发生。巨噬细胞来源的IL-6/可溶性IL-6R诱导上皮细胞中的IL-6反式信号在结肠直肠癌的发生发展中起着至关重要的作用。可溶性gp130Fc可能对预防大肠癌有效。

项目成果

Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease.

• 发表时间: 2007-11
• 期刊: Anticancer research
• 影响因子: 2
• 作者: K. Mitsuyama;S. Matsumoto;J. Masuda;Hiroshi Yamasakii;K. Kuwaki;H. Takedatsu;M. Sata

IL6トランスシグナリングを介した大腸発癌過程における粘膜マクロファージの重要性

粘膜巨噬细胞在 IL6 转信号介导的结直肠癌发生中的重要性

• 发表时间: 2008
• 作者: Satoshi Matsumoto;Mayuko Yamamoto;Keiichi Mitsuyama;Stefan Rose-John
• 通讯作者: Stefan Rose-John

腸内細菌による大腸粘膜樹状細胞のTNFαconverting enzyme (TACE)の発現誘導とTCRβ/p53二重欠損マウスにおける大腸発癌の関連性

肠道细菌诱导结肠粘膜树突状细胞TNFα转换酶（TACE）表达与TCRβ/p53双缺陷小鼠结肠癌发生的关系

• 发表时间: 2009
• 作者: Mayuko Yamamoto;Satoshi Matsumoto;Keiichi Mitsuyama;Masanobu Nanno
• 通讯作者: Masanobu Nanno

Colitis-associated cancer発症過程におけるIL6トランスシグナリングの重要性と粘膜マクロファージ

IL6转信号和粘膜巨噬细胞在结肠炎相关癌症发生过程中的重要性

• 发表时间: 2008
• 作者: 松本敏;光山慶一;山本真悠子
• 通讯作者: 山本真悠子

Gut microflora: a new target for therapeutic approaches in inflammatory bowel disease

肠道菌群：炎症性肠病治疗方法的新目标

• DOI: 10.1517/14728222.12.3.301
• 发表时间: 2008
• 期刊: Expert Opinion on Therapeutic Targets
• 影响因子: 5.8
• 作者: K. Mitsuyama;M. Sata
• 通讯作者: M. Sata