Activation of JAK/STAT signalling in neurons following spinal cord injury in mice
Activation of JAK/STAT signalling in neurons following spinal cord injury in mice
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DOI：
10.1111/j.1471-4159.2005.03559.x
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发表时间：
2006-02-01
影响因子：
4.7
通讯作者：
Yoshida, J
中科院分区：
文献类型：
--
作者：
Yamauchi, K;Osuka, K;Yoshida, J
Janus kinase (JAK)/signal transducer and activator of transcription （STAT）信号通路是细胞对细胞因子的反应中信号从细胞表面传导到细胞核的重要途径之一。在本研究中，我们研究了小鼠脊髓损伤（SCI）后JAK1、STAT3、磷酸化(p)-Tyr1022/1023-JAK1、p- tyr705 -STAT3和白细胞介素-6 （IL-6）的时间变化和细胞位置。Western blot分析显示，JAK1 Tyr1022/1023位点从SCI后6小时开始显著磷酸化，12小时达到峰值，之后逐渐降低，同时STAT3 Tyr705位点磷酸化，且磷酸化过程相似。ELISA分析显示，损伤后脊髓IL-6浓度也从3 h开始显著升高，12 h达到峰值，随后逐渐降低。免疫组化结果显示，脊髓损伤后12 h， p-Tyr1022/1023-JAK1、p-Tyr705-STAT3和IL-6主要在前角神经元中表达。用JAK抑制剂AG-490预处理，在脊髓损伤后12小时抑制JAK1和STAT3的磷酸化，减少运动功能的恢复。这些结果提示，脊髓损伤急性期主要在受损脊髓神经元中产生IL-6，激活JAK/STAT通路，该通路可能参与神经元对脊髓损伤的反应。
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway is one of the most important in transducing signals from the cell surface to the nucleus in response to cytokines. In the present study, we investigated chronological alteration and cellular location of JAK1, STAT3, phosphorylated (p)-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and interleukin-6 (IL-6) following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12 h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at Tyr705 with a similar time course. ELISA analysis showed the concentration of IL-6 in injured spinal cord to also significantly increase from 3 h after SCI, peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and IL-6 to be mainly expressed in neurons of the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG-490, suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery of motor functions. These findings suggest that SCI at the acute stage produces IL-6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT pathway, and that this pathway may be involved with neuronal response to SCI.