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

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。

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.