Sciatic nerve injury affects quality of life. Many immune cells and inflammatory cytokines have been reported to be involved in sciatic nerve injury, but little is known about the ligands and receptors that trigger inflammatory responses. By using a modified sciatic nerve clamp injury method, we found that the recruitment of Schwann cells and the inflammatory response were enhanced after sciatic nerve injury. Toll‐like receptor 4 (TLR4), one of the major members of the TLR family, is highly expressed in Schwann cells. Under certain conditions, myeloid differentiation protein 2 (MD2) binds to TLR4 on the membrane and plays important roles in the inflammatory response. The reductions in the recruitment of Schwann cells and the inflammatory response induced by the blockade of TLR4 or MD2 suggest that TLR4 and MD2 are involved in sciatic nerve injury. What are the endogenous signals that activate the inflammatory response? A large number of free saturated fatty acids (SFAs) are released from Schwann cells, adipocytes and the blood after sciatic nerve injury. Liang et al reported that Schwann cells can be stimulated by palmitic acid (PA). Here, we found that the expression and secretion of TNF‐α and IL‐6 were enhanced by PA treatment. Moreover, PA activated TLR4 signalling pathway‐related proteins and stimulated a strong association between TLR4 and MD2. Blocking TLR4 or MD2 reversed the PA‐induced inflammatory response and TLR4 downstream signalling pathway. Thus, we speculated that SFAs act as endogenous ligands that activate TLR4/MD2, thus triggering Schwann cell inflammation during sciatic nerve injury.

中文翻译：

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饱和脂肪酸激活雪旺细胞中的炎症信号传导途径：对坐骨神经损伤的影响。

坐骨神经损伤影响生活质量。据报道，许多免疫细胞和炎性细胞因子都参与了坐骨神经损伤，但是对于触发炎症反应的配体和受体知之甚少。通过使用改良的坐骨神经钳夹伤方法，我们发现坐骨神经损伤后雪旺氏细胞的募集和炎症反应得以增强。Toll样受体4（TLR4）是TLR家族的主要成员之一，在雪旺氏细胞中高表达。在某些条件下，髓样分化蛋白2（MD2）与膜上的TLR4结合并在炎症反应中起重要作用。雪旺氏细胞募集的减少和由TLR4或MD2的阻断引起的炎症反应的减少表明TLR4和MD2参与坐骨神经损伤。激活炎症反应的内源性信号是什么？坐骨神经损伤后，从雪旺氏细胞，脂肪细胞和血液中释放出大量的游离饱和脂肪酸（SFA）。Liang等人报道，许旺细胞可以被棕榈酸（PA）刺激。在这里，我们发现PA处理可增强TNF-α和IL-6的表达和分泌。此外，PA激活了TLR4信号通路相关蛋白，并刺激了TLR4和MD2之间的强关联。阻断TLR4或MD2可逆转PA诱导的炎症反应和TLR4下游信号通路。因此，我们推测SFAs是激活TLR4 / MD2的内源性配体，从而在坐骨神经损伤期间引发雪旺细胞炎症。