Medical Faculty, Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University, Universit a tsstr. 1, D-40225 Dusseldorf, Germany,
Biol Chem. 2013 Sep;394(9):1145-61. doi: 10.1515/hsz-2013-0166.
The pleiotropic physiological functions of interleukin (IL-)6 type cytokines range from embryonic development and tissue homoeostasis to neuronal development and T cell differentiation. In contrast, imbalance of the well-controlled cytokine signaling network leads to chronic inflammatory diseases and cancer. IL-6 and IL-11 both signal through a homodimer of the ubiquitously expressed β-receptor glycoprotein 130 (gp130). Specificity is gained through an individual IL-6/IL-11 α-receptor, which does not directly participate in signal transduction, although the initial cytokine binding event to the α-receptor leads to the final complex formation with the β-receptors. Both cytokines activate the same downstream signaling pathways, which are predominantly the mitogen-activated protein kinase (MAPK)-cascade and the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. However, recent studies have highlighted divergent roles of the two related cytokines. Here, we will discuss how the biochemical similarities are translated into unique and non-redundant functions of IL-6 and IL-11 in vivo and illustrate strategies for cytokine-specific therapeutic intervention.
白细胞介素 (IL-)6 型细胞因子具有多种生理功能，范围从胚胎发育和组织稳态到神经元发育和 T 细胞分化。相比之下，细胞因子信号网络的失衡会导致慢性炎症性疾病和癌症。IL-6 和 IL-11 均通过普遍表达的β-受体糖蛋白 130 (gp130) 同源二聚体发出信号。特异性是通过单独的 IL-6/IL-11 α-受体获得的，该受体不直接参与信号转导，尽管最初与 α-受体的细胞因子结合事件导致最终与 β-受体形成复合物。两种细胞因子激活相同的下游信号通路，主要是丝裂原激活的蛋白激酶 (MAPK) 级联和 Janus 激酶/信号转导和转录激活因子 (Jak/STAT) 途径。然而，最近的研究强调了两种相关细胞因子的不同作用。在这里，我们将讨论生化相似性如何转化为 IL-6 和 IL-11 在体内的独特且非冗余功能，并说明针对细胞因子的特异性治疗干预策略。
