Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Neurosci Lett. 2010 Mar 19;472(2):104-8. doi: 10.1016/j.neulet.2010.01.061. Epub 2010 Feb 1.
The interleukin-6 (IL-6) family of cytokines is thought to be involved in the development and regeneration of peripheral nerves; however, their roles in myelination remain unclear. In this study, we examined the effects of IL-6 on the expression of genes for compact myelin proteins using Schwann cell cultures prepared by multiple explantation of adult rat sciatic nerves. In semi-quantitative reverse transcription-polymerase chain reaction analysis, stimulation of Schwann cells with IL-6 significantly increased the mRNA level of peripheral myelin protein 22 (PMP22), but not those of myelin protein zero and myelin basic protein. The increase in PMP22 mRNA was markedly suppressed by AG490, a Janus kinase 2 (JAK2) inhibitor, but not significantly by PD098059, a mitogen-activated protein kinase inhibitor. Immunocytochemical staining revealed that IL-6 enhanced immunoreactivities for the phosphorylated forms of both JAK2 and signal transducer and activator of transcription 3 (STAT3), as well as that for PMP22. These results indicate that IL-6 can enhance PMP22 production in Schwann cells via a JAK2-dependent pathway by probably activating STAT3 and thus may contribute to myelination.
白细胞介素-6（IL-6）家族细胞因子被认为参与外周神经的发育和再生；然而，它们在髓鞘形成中的作用尚不清楚。在这项研究中，我们使用通过成年大鼠坐骨神经多次外植培养制备的雪旺细胞培养物，检查了 IL-6 对髓鞘蛋白基因表达的影响。在半定量逆转录聚合酶链反应分析中，IL-6 刺激雪旺细胞显著增加了外周髓鞘蛋白 22（PMP22）的 mRNA 水平，但不增加髓鞘蛋白零和髓鞘碱性蛋白的 mRNA 水平。Janus 激酶 2（JAK2）抑制剂 AG490 明显抑制 PMP22 mRNA 的增加，但丝裂原活化蛋白激酶抑制剂 PD098059 则没有明显抑制。免疫细胞化学染色显示，IL-6 增强了 JAK2 和信号转导子和转录激活子 3（STAT3）的磷酸化形式以及 PMP22 的免疫反应性。这些结果表明，IL-6 可以通过可能激活 STAT3 的 JAK2 依赖性途径增强雪旺细胞中的 PMP22 产生，从而可能有助于髓鞘形成。
