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IL-6/IL-6 receptor system and its role in physiological and pathological conditions

机译：IL-6 / IL-6受体系统及其在生理和病理状况中的作用

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摘要

IL (interleukin)-6, which was originally identified as a B-cell differentiation factor, is a multifunctional cytokine that regulates the immune response, haemopoiesis, the acute phase response and inflammation. IL-6 is produced by various types of cell and influences various cell types, and has multiple biological activities through its unique receptor system. IL-6 exerts its biological activities through two molecules: IL-6R (IL-6 receptor) and gp130. When IL-6 binds to mIL-6R (membrane-bound form of IL-6R), homodimerization of gp130 is induced and a high-affinity functional receptor complex of IL-6, IL-6R and gp130 is formed. Interestingly, sIL-6R (soluble form of IL-6R) also binds with IL-6, and the IL-6-sIL-6R complex can then form a complex with gp130. The homodimerization of receptor complex activates JAKs (Janus kinases) that then phosphorylate tyrosine residues in the cytoplasmic domain of gp130. The gp130-mediated JAK activation by IL-6 triggers two main signalling pathways: the gp130 Tyr 759-derived SHP-2 (Src homology domain-containing protein tyrosine phosphatase-2)/ERK (extracellular-signal-regulated kinase) MAPK (mitogen-activated protein kinase) pathway and the gp130 YXXQ-mediated JAK/STAT (signal transducer and activator of transcription) pathway. Increased IL-6 levels are observed in several human inflammatory diseases, such as rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis. IL-6 is also critically involved in experimentally induced autoimmune diseases. All clinical findings and animal models suggest that IL-6 plays a number of critical roles in the pathogenesis of autoimmune diseases. In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6.
机译：IL（白介素）-6，最初被确定为B细胞分化因子，是一种多功能的细胞因子，可调节免疫反应，造血作用，急性期反应和炎症。 IL-6由各种类型的细胞产生并影响各种细胞类型，并通过其独特的受体系统具有多种生物学活性。 IL-6通过两个分子发挥其生物学活性：IL-6R（IL-6受体）和gp130。当IL-6与mIL-6R（IL-6R的膜结合形式）结合时，会引起gp130的二聚化，并形成IL-6，IL-6R和gp130的高亲和力功能受体复合物。有趣的是，sIL-6R（IL-6R的可溶形式）也与IL-6结合，然后IL-6-sIL-6R复合物可以与gp130形成复合物。受体复合物的同二聚化激活JAK（Janus激酶），然后将gp130胞质域中的酪氨酸残基磷酸化。 IL-6介导的gp130介导的JAK激活触发了两个主要的信号通路：gp130 Tyr 759衍生的SHP-2（含Src同源域的蛋白酪氨酸磷酸酶2）/ ERK（细胞外信号调节激酶）MAPK（促分裂原）激活蛋白激酶）途径和gp130 YXXQ介导的JAK / STAT（信号转导和转录激活剂）途径。在几种人类炎性疾病，例如类风湿性关节炎，Castleman病和全身性幼年特发性关节炎中，观察到IL-6水平升高。 IL-6也至关重要地参与了实验诱发的自身免疫性疾病。所有临床发现和动物模型均表明，IL-6在自身免疫性疾病的发病机理中起许多关键作用。在本综述中，我们首先概述IL-6 / IL-6R系统和IL-6信号转导，然后继续讨论IL-6的生理和病理作用。

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