Local Application of Interleukin-6 to the Dorsal Root Ganglion Induces Tumor Necrosis Factor-Alpha in the Dorsal Root Ganglion and Results in Apoptosis of the Dorsal Root Ganglion Cells
Local Application of Interleukin-6 to the Dorsal Root Ganglion Induces Tumor Necrosis Factor-Alpha in the Dorsal Root Ganglion and Results in Apoptosis of the Dorsal Root Ganglion Cells
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DOI：
10.1097/brs.0b013e3181e7f4a9
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发表时间：
2011-05-20
期刊：
影响因子：
3
通讯作者：
Olmarker, Kjell
中科院分区：
文献类型：
--
作者：
Murata, Yasuaki;Rydevik, Bjorn;Olmarker, Kjell
研究设计。采用电镜和免疫组化技术，研究暴露于髓核的背根神经节（DRG）表面组织反应形成背后的细胞凋亡机制，特别是白细胞介素6（IL-6）的作用。 目的。研究IL-6对DRG的作用。背景数据总结。据报道，髓核细胞能够产生促炎细胞因子，包括肿瘤坏死因子-α（TNF-α）和IL-6。最近，观察到髓核的局部应用引起了背根神经节表面的特征性组织反应。这种变化是由于 DRG 神经元凋亡所致。然而，IL-6 在 DRG 神经元凋亡中的作用尚不清楚。方法。将重组 IL-6 应用在 L4 DRG 和硬脑膜之间，以模拟大鼠 L4-L5 椎间盘突出症。术后 24 小时切除 L4 DRG。使用 TNF-α 抗血清对切片进行免疫组织化学处理。此外，使用光学和电子显微镜观察标本切片以证实DRG神经元的诱导凋亡。还使用单链 DNA (ssDNA) 和 Caspase 3 的抗血清对切片进行免疫组织化学处理。结果。在应用 IL-6 部位的 DRG 周围区域观察到 TNF-α 免疫反应性。光镜和电镜观察DRG中细胞核的典型变化，表明细胞凋亡的存在。 ssDNA和Caspase 3的存在进一步增强了DRG神经元凋亡的印象。结论。 IL-6似乎在暴露于IL-6的DRG表面诱导TNF-α，并在DRG表面诱导特征性反应。因此，IL-6 可能在髓核诱导的 DRG 神经元以及 TNF-α 细胞凋亡中发挥重要作用。
Study Design. The mechanisms of apoptosis behind the formation of tissue reactions at the surface of the dorsal root ganglion (DRG) exposed to the nucleus pulposus were studied with special reference to the role of interleukin-6 (IL-6), using electron microscopy and immunohistochemistry in rats.Objective. To study the role of IL-6 on the DRG.Summary of Background Data. It has been reported that nucleus pulposus cells are capable to produce proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and IL-6. Recently, it was observed that local application of nucleus pulposus induced a characteristic tissue reaction at the surface of the DRG. This change was due to apoptosis of DRG neurons. However, the role of IL-6 is not known regarding the apoptosis of the DRG neurons.Methods. Recombinant IL-6 was applied between the L4 DRG and the dura to mimic a disc herniation of the L4-L5 disc in rats. The L4 DRGs were resected 24 hours after surgery. The sections were processed for immunohistochemistry using antisera to TNF-alpha. Furthermore, the sections of the specimens were observed using light and electron microscopy to confirm the induced apoptosis of the DRG neurons. The sections were also processed for immunohistochemistry, using antisera to single-stranded DNA (ssDNA) and Caspase 3.Results. TNF-alpha immunoreactivity was observed in the peripheral area of DRG at the site of the application of IL-6. Typical changes of the cell nuclei were observed in the DRG by light and electron microscopy, indicating the presence of apoptosis. The presence of ssDNA and Caspase 3 further enhanced the impression that there was apoptosis of the DRG neurons.Conclusion. IL-6 seemed to induce TNF-alpha at the surface of DRG exposed to IL-6 and to induce a characteristic reaction at the surface of the DRG. IL-6 may thus play an important role in nucleus pulposus-induced apoptosis of the DRG neurons as well as TNF-alpha.