PDF(Pubmed)
Abstract：
Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.
摘要：
脊髓损伤（SCI）后过度的神经炎症是神经修复过程中的主要障碍。尽管促炎巨噬细胞/小胶质细胞介导的神经炎症起着重要作用，引发神经炎症和加重因素的潜在机制尚不清楚.本研究确定了semaphorin3C（SEMA3C）在SCI后的免疫调节中的促炎作用。SEMA3C表达水平在损伤后7天(dpi)达到峰值并降低14dpi。体内和体外研究表明，巨噬细胞/小胶质细胞在局部微环境中表达SEMA3C，诱导神经炎症和促炎巨噬细胞/小胶质细胞的转化。机制实验表明RAGE/NF-κB是SEMA3C的下游靶标。抑制SEMA3C介导的RAGE信号传导显著抑制了促炎细胞因子的产生，SCI后不久巨噬细胞/小胶质细胞的反极化。此外,SEMA3C介导的RAGE信号传导的抑制表明SEMA3C/RAGE轴是保护轴突免受神经炎症的可行靶标。一起来看,我们的研究首次提供了SEMA3C通过自分泌机制在SCI中发挥免疫调节作用的实验证据.
