Department of Biomedical and Molecular Sciences, Gastrointestinal Diseases Research Unit and Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 2V7, Canada.
J Neurosci. 2012 Jan 25;32(4):1146-55. doi: 10.1523/JNEUROSCI.5343-11.2012.
Inflammation can profoundly alter the structure and function of the nervous system. Interleukin (IL)-17 has been implicated in the pathogenesis of several inflammatory diseases associated with nervous system plasticity. However, the effects of IL-17 on the nervous system remain unexplored. Cell and explant culture techniques, immunohistochemistry, electrophysiology, and Ca2+ imaging were used to examine the impact of IL-17 on adult mouse sympathetic neurons. Receptors for IL-17 were present on postganglionic neurons from superior mesenteric ganglia (SMG). Supernatant from activated splenic T lymphocytes, which was abundant in IL-17, dramatically enhanced axonal length of SMG neurons. Importantly, IL-17-neutralizing antiserum abrogated the neurotrophic effect of splenocyte supernatant, and incubation of SMG neurons in IL-17 (1 ng/ml) significantly potentiated neurite outgrowth. The neurotrophic effect of IL-17 was accompanied by inhibition of voltage-dependent Ca2+ influx and was recapitulated by incubation of neurons in a blocker of N-type Ca2+ channels (ω-conotoxin GVIA; 30 nM). IL-17-induced neurite outgrowth in vitro appeared to be independent of glia, as treatment with a glial toxin (AraC; 5 μM) did not affect the outgrowth response to IL-17. Moreover, application of the cytokine to distal axons devoid of glial processes enhanced neurite extension. An inhibitor of the NF-κB pathway (SC-514; 20 μM) blocked the effects of IL-17. These data represent the first evidence that IL-17 can act on sympathetic somata and distal neurites to enhance neurite outgrowth, and identify a novel potential role for IL-17 in the neuroanatomical plasticity that accompanies inflammation.
炎症可以深刻改变神经系统的结构和功能。白细胞介素 (IL)-17 与几种与神经系统可塑性相关的炎症性疾病的发病机制有关。然而，IL-17 对神经系统的影响仍未得到探索。细胞和外植体培养技术、免疫组织化学、电生理学和 Ca2+ 成像用于研究 IL-17 对成年小鼠交感神经元的影响。肠系膜上神经节 (SMG) 的节后神经元存在 IL-17 受体。富含 IL-17 的激活脾 T 淋巴细胞的上清液显著增强了 SMG 神经元的轴突长度。重要的是，IL-17 中和抗血清消除了脾细胞上清液的神经营养作用，并且 SMG 神经元在 IL-17（1ng/ml）中孵育显著增强了神经突生长。IL-17 的神经营养作用伴随着电压依赖性 Ca2+ 内流的抑制，并且通过在神经元中孵育 N 型 Ca2+ 通道阻断剂（ω-芋螺毒素 GVIA；30nM）来再现。IL-17 在体外诱导的神经突生长似乎独立于神经胶质，因为用神经胶质毒素（AraC；5μM）处理不会影响对 IL-17 的生长反应。此外，将细胞因子应用于没有神经胶质突起的远端轴突增强了神经突延伸。NF-κB 途径抑制剂（SC-514；20μM）阻断了 IL-17 的作用。这些数据代表了第一个证据，表明 IL-17 可以作用于交感神经元体和远端神经突以增强神经突生长，并确定了 IL-17 在伴随炎症的神经解剖可塑性中的新的潜在作用。
