可溶性白细胞介素 6 受体：炎症的先进治疗选择。
The Soluble Interleukin 6 Receptor: Advanced Therapeutic Options in Inflammation.
机构信息
Institute of Biochemistry, University of Kiel, Germany.
出版信息
Clin Pharmacol Ther. 2017 Oct;102(4):591-598. doi: 10.1002/cpt.782. Epub 2017 Jul 29.
Interleukin (IL)-6 binds to IL-6R and the complex of IL-6 and IL-6R associates with the receptor subunit gp130, which initiates signaling. gp130 is expressed on all cells. IL-6R is cleaved by the ADAM17, generating a soluble IL-6R (sIL-6R). The sIL-6R binds IL-6 and the complex of IL-6 and sIL-6R binds to gp130 even on cells that do not express IL-6R. This process, which has been called IL-6 trans-signaling, increases the spectrum of target cells for IL-6. We generated a protein, sgp130Fc, which inhibits IL-6 trans-signaling without affecting IL-6 classic signaling. Using the sgp130Fc protein we demonstrated that IL-6 classic signaling is antiinflammatory and protective, whereas IL-6 trans-signaling is proinflammatory. Blocking IL-6 trans-signaling does not compromise the defense of the body against bacterial infections. We suggest that sgp130Fc is a superior agent as compared to IL-6 or IL-6R antibodies to block IL-6. The sgp130Fc protein is in phase II clinical trials.
白细胞介素 (IL)-6 与 IL-6R 结合，IL-6 和 IL-6R 的复合物与受体亚基 gp130 结合，从而启动信号转导。gp130 表达于所有细胞上。IL-6R 可被 ADAM17 切割，产生可溶性 IL-6R（sIL-6R）。sIL-6R 与 IL-6 结合，IL-6 和 sIL-6R 的复合物与 gp130 结合，即使在不表达 IL-6R 的细胞上也是如此。这一过程被称为 IL-6 转导信号，增加了 IL-6 的靶细胞谱。我们生成了一种蛋白质 sgp130Fc，它可以抑制 IL-6 转导信号，而不影响 IL-6 经典信号。使用 sgp130Fc 蛋白，我们证明了 IL-6 经典信号具有抗炎和保护作用，而 IL-6 转导信号则具有促炎作用。阻断 IL-6 转导信号不会损害机体对抗细菌感染的防御能力。我们认为，与 IL-6 或 IL-6R 抗体相比，sgp130Fc 是一种更优越的阻断 IL-6 的药物。sgp130Fc 蛋白正在进行 II 期临床试验。
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