Müllberg J, Geib T, Jostock T, Hoischen S H, Vollmer P, Voltz N, Heinz D, Galle P R, Klouche M, Rose-John S
I. Medizinische Klinik, Abteilung Pathophysiologie, Johannes Gutenberg-Universität Mainz, Mainz, Germany.
J Immunol. 2000 May 1;164(9):4672-7. doi: 10.4049/jimmunol.164.9.4672.
The genome of human herpes virus 8, which is associated with Kaposi's sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling has been shown for hematopoietic progenitor cells, endothelial cells, and smooth muscle cells. In this paper we show that purified recombinant vIL-6 binds to gp130 and stimulates primary human smooth muscle cells. IL-6R fails to bind vIL-6 and is not involved in its signaling. A Fc fusion protein of gp130 turned out to be a potent inhibitor of vIL-6. Our data demonstrate that vIL-6 is the first cytokine which directly binds and activates gp130. This property points to a possible role of this viral cytokine in the pathophysiology of human herpes virus 8.
与卡波西肉瘤相关的人类疱疹病毒8基因组编码的蛋白质与细胞因子和趋化因子相似，包括白细胞介素-6的同源物。尽管这些病毒蛋白的功能尚不清楚，但它们可能具有调节免疫系统的潜力。对于病毒白细胞介素-6（vIL-6），已证明它能刺激依赖白细胞介素-6的细胞，这表明其利用了白细胞介素-6受体（IL-6R）系统。白细胞介素-6与IL-6R结合，IL-6/IL-6R复合物与gp130结合，gp130二聚化并启动细胞内信号传导。仅表达gp130而不表达IL-6R的细胞不能被白细胞介素-6刺激，除非存在可溶性形式的IL-6R。造血祖细胞、内皮细胞和平滑肌细胞都已显示出这种信号传导类型。在本文中，我们表明纯化的重组vIL-6与gp130结合并刺激原代人平滑肌细胞。IL-6R不能结合vIL-6，也不参与其信号传导。结果表明，gp130的Fc融合蛋白是vIL-6的有效抑制剂。我们的数据表明，vIL-6是第一种直接结合并激活gp130的细胞因子。这一特性表明这种病毒细胞因子在人类疱疹病毒8的病理生理学中可能发挥作用。
