Department of Anatomy, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran; Department of Anatomy, School of Medicine, Qom University of Medical Sciences, Qom, Iran.
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Chem Neuroanat. 2019 Apr;97:1-8. doi: 10.1016/j.jchemneu.2019.01.011. Epub 2019 Jan 28.
After spinal cord injury (SCI) local inflammation is induced following secretion of interleukin-1beta (IL-1β) and IL-18. It has been described that the secretion of IL-1β and IL-18 is mediated by a cytoplasmic multiprotein complex, termed inflammasome. Mesenchymal stem cells (MSCs) have been extensively used for treating inflammatory diseases in which they showed immunomodulation characteristics. We utilized the anti-inflammatory potential of Wharton's jelly mesenchymal stem cells (WJ-MSCs) to target inflammasome complex in rat SCI model. Real time-polymerase chain reaction, western blotting, and ELISA assay were done one week after SCI to measure the expression of the inflammasome components including NLRP1, ASC, and active caspase-1 as well as IL-1β, IL-18, and tumor necrosis factor-α (TNF-α). The histologic alteration and hind-limb locomotion were evaluated three weeks after injury by nissl staining and Basso, Beattie, Bresnahan (BBB), respectively. Our results showed that WJ-MSCs transplantation significantly decreased the SCI-induced expression of the evaluated factors in both mRNA and protein levels. In addition, WJ-MSCs significantly increased the number of normal-appearance neurons in the ventral horn of spinal cord. Noteworthy, these effects resulted in a significant improvement of motor function recovery. We conclude that inflammasome inhibition may be one of the mechanisms for the anti-inflammatory effect of MSCs in the SCI.
脊髓损伤 (SCI) 后，白细胞介素-1β (IL-1β) 和白细胞介素-18 的分泌会引起局部炎症。据描述，IL-1β 和 IL-18 的分泌是由一种称为炎性小体的细胞质多蛋白复合物介导的。间充质干细胞 (MSCs) 已被广泛用于治疗炎症性疾病，它们表现出免疫调节特性。我们利用 Wharton 胶间充质干细胞 (WJ-MSCs) 的抗炎潜力，在大鼠 SCI 模型中靶向炎性小体复合物。SCI 后一周通过实时聚合酶链反应、蛋白质印迹和 ELISA 检测来测量炎性小体成分（包括 NLRP1、ASC 和活性半胱天冬酶-1）以及 IL-1β、IL-18 和肿瘤坏死因子-α (TNF-α) 的表达。损伤后三周通过尼氏染色和 Basso、Beattie、Bresnahan (BBB) 评估组织学改变和后肢运动。我们的结果表明，WJ-MSCs 移植显著降低了 SCI 诱导的评估因子在 mRNA 和蛋白水平上的表达。此外，WJ-MSCs 显著增加了脊髓腹角中正常形态神经元的数量。值得注意的是，这些效果导致运动功能恢复显著改善。我们得出结论，炎性小体抑制可能是 MSC 在 SCI 中抗炎作用的机制之一。
