Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease.
Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease.
复制标题
DOI：
--
复制
发表时间：
2007-11
影响因子：
2
通讯作者：
K. Mitsuyama;S. Matsumoto;J. Masuda;Hiroshi Yamasakii;K. Kuwaki;H. Takedatsu;M. Sata
中科院分区：
文献类型：
--
作者：
K. Mitsuyama;S. Matsumoto;J. Masuda;Hiroshi Yamasakii;K. Kuwaki;H. Takedatsu;M. Sata
白细胞介素-6（IL-6）是一种多效性细胞因子，在免疫和炎症反应中起重要作用。IL-6首先与IL-6受体（IL-6 R）结合，然后该复合物与gp 130结合，诱导二聚化并通过信号转导子和转录激活子-3（STAT 3）启动信号传导。值得注意的是，可溶性IL-6受体（sIL-6 R）和IL-6的组合刺激仅表达gp 130而不表达IL-6 R的细胞，这一过程称为反式信号传导。相反，可溶性gpl 30（sgpl 30）充当反式信号传导的天然抑制剂。累积的证据强烈支持炎症性肠病（IBD）的发展和持续依赖于IL-6介导的粘膜T细胞上的STAT 3活化的假设。本文综述了针对IBD患者IL-6/STAT 3通路的治疗策略，包括涉及抗IL-6受体抗体和可溶性gp 130 Fc的策略。
Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune and inflammatory reactions. IL-6 first binds to the IL-6 receptor (IL-6R), this complex then associates with gp130, inducing dimerization and the initiation of signaling through signal transducer and activator of transcription-3 (STAT3). Notably, the combination of soluble IL-6 receptor (sIL-6R) and IL-6 stimulates cells that only express gp130 and not IL-6R, a process known as trans-signaling. In contrast, soluble gpl30 (sgp130) serves as a natural inhibitor of trans-signaling. Accumulated evidence strongly supports the hypothesis that the development and perpetuation of inflammatory bowel disease (IBD) relies on IL-6-mediated STAT3 activation on mucosal T-cells. This review looks at therapeutic strategies targeting the IL-6/STAT3 pathway in patients with IBD, including strategies involving the anti-IL-6 receptor antibody and soluble gp130Fc.