Activation and regulation of the disease-related IL-6/STAT3 signaling

疾病相关 IL-6/STAT3 信号传导的激活和调节

• 批准号: 20390017
• 负责人: MATSUDA Tadashi
• 金额: $ 12.4万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390017/
• 关键词: 免疫; がん; シグナル伝達; サイトカイン; IL-6; STAT3; 自己免疫疾患; 癌; 炎症

Since we cloned interleukin-6 (IL-6) as B cell stimulatory factor 2 in 1986, IL-6 has been reported to influence cell proliferation, differentiation, and survival as well as mature cell functions. Signal transducer and activator of transcription 3 (STAT3) is a key molecule to mediate IL-6-induced cellular events. Indeed, STAT3 is activated in many tumor tissues, and the dimmer of STAT3 promotes cellular transformation, indicating that STAT3 itself can act as a proto-oncogene. In addition to oncogenesis, IL-6/STAT3 axis influences host immune systems. For example, IL-6/STAT3 axis is involved in the Toll-like receptor signaling pathways, the development and maturation of dendritic cells, and the differentiation of Th17 T-cell subset. These facts are likely to suggest that manipulation of IL-6/STAT3 signals could be suitable target for a variety of disease such as cancer and autoimmune diseases. We have energetically examined regulatory mechanisms of IL-6/STAT3-mediated signal transduction for the development of novel therapeutic strategies.

自从1986年我们克隆了白细胞介素-6（IL-6）作为B细胞刺激因子2以来，已经报道IL-6影响细胞增殖、分化和存活以及成熟细胞功能。信号转导子和转录激活子3（STAT 3）是介导IL-6诱导的细胞事件的关键分子。事实上，STAT 3在许多肿瘤组织中被激活，STAT 3的二聚体促进细胞转化，表明STAT 3本身可以作为原癌基因。除了肿瘤发生，IL-6/STAT 3轴影响宿主免疫系统。例如，IL-6/STAT 3轴参与Toll样受体信号通路、树突状细胞的发育和成熟以及Th 17 T细胞亚群的分化。这些事实可能表明，IL-6/STAT 3信号的操纵可能是多种疾病如癌症和自身免疫性疾病的合适靶点。我们已经积极研究了IL-6/STAT 3介导的信号转导的调节机制，以开发新的治疗策略。

项目成果

A single polymorphic amino acid replacement in Toxoplasma gondii ROP16 influences its direct Stat3 activation

弓形虫 ROP16 中的单个多态性氨基酸替换影响其直接 Stat3 激活

• 发表时间: 2009
• 期刊: J. Exp. Med. 206
• 作者: Yamamoto M.;D. M. Standley S. Takashima H. Saiga M. Okuyama H. Kayama E. Kubo;H. Ito M. Takaura T. Matsuda D. Soldati-Favre;K. Takada
• 通讯作者: K. Takada

低分子量二重特異性ホスファターゼDUSP3によるSTAT3活性制御機構の解析

低分子双特异性磷酸酶DUSP3对STAT3活性的调控机制分析

• 发表时间: 2010
• 作者: 関根勇一;ほか
• 通讯作者: ほか

EJC構成タンパク質Y14, MAGOHによるSTAT3活性の制御

EJC 成分蛋白 Y14、MAGOH 对 STAT3 活性的调节

• 发表时间: 2010
• 作者: 志賀要;ほか
• 通讯作者: ほか

BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-κB activation

• DOI: 10.1016/j.febslet.2010.01.060
• 发表时间: 2010-03-05
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Ikeda, Osamu;Miyasaka, Yuto;Matsuda, Tadashi
• 通讯作者: Matsuda, Tadashi

Wnt/β-カテニンシグナルにおけるZIPKとNLKの機能的相互作用の解析

ZIPK 和 NLK 在 Wnt/β-catenin 信号传导中的功能相互作用分析

• 发表时间: 2010
• 作者: 中筋美紗;ほか
• 通讯作者: ほか