Scheller Jürgen, Schuster Björn, Hölscher Christoph, Yoshimoto Takayuki, Rose-John Stefan
Institut für Biochemie, Christian-Albrechts Universität zu Kiel, Olshausenstr.40, D-24098 Kiel, Germany.
Biochem Biophys Res Commun. 2005 Jan 28;326(4):724-8. doi: 10.1016/j.bbrc.2004.11.098.
Soluble gp130 is the natural inhibitor of trans-signaling mediated by the soluble IL-6/IL-6R complex. In mouse models, recombinant sgp130 has been successfully applied for the treatment of diseases that are triggered and maintained by soluble IL-6R like Crohn's disease, peritonitis, rheumatoid arthritis, and colon cancer. The novel heterodimeric cytokine IL-27 (p28/EBV-induced gene 3) has been shown to act via a heterodimeric receptor complex of gp130 and the WSX-1 receptor, and to co-regulate the Th(1) immune response after infection. Therefore, we have tested the potential of the recombinant sgp130-Fc protein to also inhibit signaling-mediated IL-27. Here we show that sgp130-Fc does not interfere with IL-27 signaling. We therefore conclude that IL-27 does not bind with high affinity to gp130.
可溶性gp130是可溶性IL-6/IL-6R复合物介导的转信号传导的天然抑制剂。在小鼠模型中,重组sgp130已成功应用于治疗由可溶性IL-6R引发和维持的疾病,如克罗恩病、腹膜炎、类风湿性关节炎和结肠癌。新型异二聚体细胞因子IL-27(p28/EB病毒诱导基因3)已被证明通过gp130和WSX-1受体的异二聚体受体复合物发挥作用,并在感染后共同调节Th(1)免疫反应。因此,我们测试了重组sgp130-Fc蛋白抑制IL-27信号传导的潜力。在此我们表明,sgp130-Fc不会干扰IL-27信号传导。因此我们得出结论,IL-27不会与gp130高亲和力结合。