Hirota H, Kiyama H, Kishimoto T, Taga T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
J Exp Med. 1996 Jun 1;183(6):2627-34. doi: 10.1084/jem.183.6.2627.
In this study we aimed to examine a role for interleukin 6 (IL-6) and its receptor (IL-6R) in peripheral nerve regeneration in vivo. We first observed that cultured mouse embryonic dorsal root ganglia exhibited dramatic neurite extension by simultaneous addition of IL-6 and soluble IL-6R (sIL-6R), a complex that is known to interact with and activate a signal transducing receptor component, gp130. After injury in the hypoglossal nerve in adult mice by ligation, immunoreactivity to IL-6 was upregulated in Schwann cells at the lesional site as well as in the cell bodies of hypoglossal neurons in the brain stem. In the latter, upregulation of the immunoreactivity to IL-6R was also observed. Regeneration of axotomized hypoglossal nerve in vivo was significantly retarded by the administration of anti-IL-6R antibody. Surprisingly, accelerated regeneration of the axotomized nerve was achieved in transgenic mice constitutively expressing both IL-6 and IL-6R, as compared with nontransgenic controls. These results suggest that the IL-6 signal may play an important role in nerve regeneration after trauma in vivo.
在本研究中，我们旨在探讨白细胞介素6（IL-6）及其受体（IL-6R）在体内周围神经再生中的作用。我们首先观察到，通过同时添加IL-6和可溶性IL-6R（sIL-6R），培养的小鼠胚胎背根神经节表现出显著的神经突延伸，已知该复合物可与信号转导受体成分gp130相互作用并激活它。成年小鼠舌下神经结扎损伤后，损伤部位的雪旺细胞以及脑干中舌下神经元的细胞体中，IL-6的免疫反应性上调。在后者中，也观察到IL-6R免疫反应性的上调。给予抗IL-6R抗体可显著延缓体内切断的舌下神经的再生。令人惊讶的是，与非转基因对照相比，在组成性表达IL-6和IL-6R的转基因小鼠中，切断的神经实现了加速再生。这些结果表明，IL-6信号可能在体内创伤后的神经再生中起重要作用。
