CXCL13通过CXCR5激活星形胶质细胞中JNK参与痛觉过敏

CXCL13 activates JNK in astrocytes through CXCR5 to induce pain hypersensitivity

摘要:

目的：探讨CXCL13及其受体CXCR5参与痛觉过敏的机制。方法：细胞培养和免疫荧光染色检测脊髓背角神经元中CXCL13的表达；通过转染CXCL13和CXCR5过表达质粒研究CXCL13和CXCR5的相互作用；Western Blot方法检测CXCL13重组因子刺激原代星形胶质细胞后JNK磷酸化水平变化和鞘内注射CXCL13后脊髓中JNK磷酸化水平变化；行为学检测鞘内注射JNK抑制剂SP600125对CXCL13引起的热痛觉过敏和机械性触诱发痛的影响。结果：1.体外培养的脊髓背角神经元表达并释放CXCL13。2.CXCL13分泌后与受体CXCR5结合并发生内化。3. CXCL13孵育培养的星形胶质细胞快速而短暂地激活JNK。4.鞘内注射CXCL13快速且短暂激活脊髓中的JNK。5.鞘内注射JNK抑制剂缓解了CXCL13诱导的热痛觉过敏和机械性触诱发痛。结论：CXCL13通过CXCR5激活星形胶质细胞中JNK参与痛觉过敏。

Abstract:

Objective: To explore the mechanism of CXCL13 and its receptor CXCR5underlying pain hypersensitivity. Methods: The expression of chemokine CXCL13 in spinal dorsal horn neurons was examined via dorsal horn neuron culture and immunofluorescence staining;CXCL13 and CXCR5 overexpression plasmids were transfected to clarify the interaction between CXCL13 and CXCR5; Western Blot was used to detect the phosphorylation of JNK in primary astrocytes after CXCL13 incubation or in the spinal cord after intrathecal injection of CXCL13; Behavioral test was used to check pain hypersensitivity after intrathecal injection of JNK inhibitor SP600125 and CXCL13. Result:1. In vitro cultured spinal dorsal horn neurons express and release chemokine CXCL13. 2. CXCL13 was secreted and internalized via binding to the receptor CXCR5. 3. CXCL13 rapidly and transiently activated JNK in cultured astrocytes. 4. Intrathecal injection of CXCL13 rapidly and transiently activated JNK in the spinal cord. 5. Intrathecal injection of JNK inhibitor alleviated heat hyperalgesia and mechanical allodynia induced by CXCL13. Conclusion: CXCL13 activates JNK in astrocytes through CXCR5 to induce pain hypersensitivity.