Yang Gang, Tang Wen-Yuan
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Int J Mol Med. 2017 Feb;39(2):437-445. doi: 10.3892/ijmm.2017.2848. Epub 2017 Jan 5.
Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou-ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy. The present study was carried out to examine the potential function of IL-6 in resistance to neurite growth‑inhibitory effects via regulation of the expression of growth associated protein-43 (GAP-43), myelin-associated neurite outgrowth inhibitor (Nogo-A) and its receptor (NgR). Rat dorsal root ganglion (DRG) neurons cultured in an inhibitory microenvironment mimicking injured CNS were used to investigate the effects of IL-6 on the outgrowth of neuronal processes. Additionally, IL-6 was subarachnoidally injected into rats to establish a spinal cord injury (SCI) model, and the neurobehavioral manifestations and neural morphology were subsequently evaluated to determine the effect of IL-6 on neural regeneration. Finally, the potential molecular mechanisms of IL-6-mediated rege-neration and functional recovery following CNS injury are discussed. The results of the present study demonstrated that the in vitro administration of IL-6 enhanced the neurite outgrowth of DRG neurons in a dose-dependent manner via resisting the inhibitory function of myelin proteins. All doses of the IL-6 subarachnoid injection improved the Basso, Beattie and Bresnahan scores following SCI, with a large number of axonal sproutings observed at the spinal lesion site, and several sprouting fibers being elongated and bypassing the lesion and entered the caudal spinal cord. Additionally, a significantly increased density area of diaminobenzidine-labeled neural fiber was observed in rats that received a subarachnoid injection of IL-6, and the rats exhibited increased expression of GAP-43 and decreased expression of Nogo-A. In conclusion, the results of the present study indicated that IL-6 interferes with the inhibitory functions of myelin proteins by upregulating the expression of GAP-43 and simultaneously downregulating the expression of Nogo-A and NgR to promote axonal sprouting and functional recovery following SCI.
白细胞介素-6（IL-6）最初被发现是一种在中枢神经系统（CNS）损伤后促成继发性病理和炎症反应的因子。然而，越来越多的证据表明，IL-6还通过促进轴突发芽参与CNS损伤后的功能和结构恢复。这表明IL-6在CNS损伤中可能具有双重作用。然而，IL-6在神经损伤中的确切功能以及相应的潜在机制仍是有争议的话题。本研究旨在通过调节生长相关蛋白43（GAP-43）、髓磷脂相关神经突生长抑制因子（Nogo-A）及其受体（NgR）的表达，研究IL-6在抵抗神经突生长抑制作用方面的潜在功能。使用在模拟损伤CNS的抑制性微环境中培养的大鼠背根神经节（DRG）神经元来研究IL-6对神经突生长的影响。此外，将IL-6蛛网膜下腔注射到大鼠体内以建立脊髓损伤（SCI）模型，随后评估神经行为表现和神经形态，以确定IL-6对神经再生的影响。最后，讨论了IL-6介导的CNS损伤后再生和功能恢复的潜在分子机制。本研究结果表明，体外给予IL-6通过抵抗髓磷脂蛋白的抑制功能，以剂量依赖的方式增强了DRG神经元的神经突生长。所有剂量的IL-6蛛网膜下腔注射均改善了SCI后的Basso、Beattie和Bresnahan评分，在脊髓损伤部位观察到大量轴突发芽，并且有几条发芽纤维伸长并绕过损伤部位进入尾侧脊髓。此外，在接受蛛网膜下腔注射IL-6的大鼠中观察到二氨基联苯胺标记的神经纤维密度区域显著增加，并且大鼠表现出GAP-43表达增加和Nogo-A表达降低。总之，本研究结果表明，IL-6通过上调GAP-43的表达并同时下调Nogo-A和NgR的表达来干扰髓磷脂蛋白的抑制功能，从而促进SCI后的轴突发芽和功能恢复。
