IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6.
IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6.
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DOI：
10.7150/ijbs.4989
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发表时间：
2012
影响因子：
9.2
通讯作者：
Rose-John S
中科院分区：
文献类型：
--
作者：
Rose-John S
白细胞介素-6（IL-6）是一种具有多种活性的细胞因子。它具有调节免疫系统和神经系统的功能。此外，IL-6参与肝再生和身体的代谢控制。在靶细胞上，IL-6与80 kDa IL-6受体（IL-6 R）结合。IL-6和IL-6 R的复合物与第二种蛋白质gp 130结合，gp 130随后二聚化并启动细胞内信号传导。尽管gp 130在所有细胞上表达，但IL-6 R仅存在于体内少数细胞上，包括肝细胞和一些白细胞。不表达IL-6 R的细胞不能响应细胞因子，因为单独的gp 130对IL-6没有可测量的亲和力。有趣的是，包含受体的细胞外部分的可溶形式的IL-6 R（sIL-6 R）可以以与膜结合的IL-6 R相似的亲和力结合IL-6。IL-6和sIL-6 R的复合物可以结合不表达IL-6 R且对IL-6无反应的细胞上的gp 130。这个过程被称为trans-signaling。在这里，我将回顾已发表的证据表明，IL-6反式信号是促炎，而经典的IL-6信号通过膜结合的IL-6 R是需要的细胞因子的再生或抗炎活性。此外，IL-6生物学的详细知识对旨在阻断细胞因子IL-6的治疗策略具有重要影响。
Interleukin-6 (IL-6) is a cytokine with many activities. It has functions in the regulation of the immune system and the nervous system. Furthermore, IL-6 is involved in liver regeneration and in the metabolic control of the body. On target cells, IL-6 binds to an 80 kDa IL-6 receptor (IL-6R). The complex of IL-6 and IL-6R associates with a second protein, gp130, which thereupon dimerizes and initiates intracellular signaling. Whereas gp130 is expressed on all cells, IL-6R is only present on few cells in the body including hepatocytes and some leukocytes. Cells, which do not express IL-6R cannot respond to the cytokine, since gp130 alone has no measurable affinity for IL-6. Interestingly, a soluble form of IL-6R (sIL-6R) comprising the extracellular portion of the receptor can bind IL-6 with a similar affinity as the membrane bound IL-6R. The complex of IL-6 and sIL-6R can bind to gp130 on cells, which do not express the IL-6R, and which are unresponsive to IL-6. This process has been called trans-signaling. Here I will review published evidence that IL-6 trans-signaling is pro-inflammatory whereas classic IL-6 signaling via the membrane bound IL-6R is needed for regenerative or anti-inflammatory activities of the cytokine. Furthermore, the detailed knowledge of IL-6 biology has important consequences for therapeutic strategies aimed at the blockade of the cytokine IL-6.
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影响因子：
64.8
作者：
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通讯作者：
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