College of Pharmacy, Anhui Medical University, Hefei, China.
Department of Orthopaedics, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Sci Rep. 2017 Mar 10;7:41779. doi: 10.1038/srep41779.
Spinal cord injury is a grave neurological disability resulting in neuron degeneration and permanent paralysis. The inflammation triggered by the injury would promote the spinal cord lesion in turn. Activated astrocytes during inflammatory response could promote glial scar formation and contribute to the progression of the spinal cord injury. Interleukin 17 (IL-17) was upregulated in inflammatory responses to contusion or compression of the spinal cord. in this study, IL-17 could induce reactive astrocytes which was indicated by a well-known hallmark glial fibrillary acidic protein (GFAP) in vitro and in vivo. Moreover, we demonstrated that the upregulation of VEGF was induced by IL-17 human astrocytoma cells. In our further investigation, IL-17 induced the expression of VEGF in spinal cord injury by activating JAK/STAT signaling pathway both in vitro and in vivo. In addition, we also found that IL-17 significantly changed tissue preservation and residual urine volumes and blood-spinal cord-barrier integrity in vivo. This newly found IL-17-JAK/STAT-VEGF axis improves our understanding of the molecular mechanism of spinal cord injury during inflammatory response and provides another potential target of spinal cord injury.
脊髓损伤是一种严重的神经功能障碍，导致神经元变性和永久性瘫痪。损伤引发的炎症反过来会促进脊髓损伤。炎症反应中激活的星形胶质细胞可促进神经胶质瘢痕形成，并促进脊髓损伤的进展。白细胞介素 17（IL-17）在脊髓挫伤或压迫的炎症反应中上调。在这项研究中，IL-17 可诱导反应性星形胶质细胞，这在体外和体内通过众所周知的神经胶质纤维酸性蛋白（GFAP）标志物得到证实。此外，我们证明了 VEGF 的上调是由 IL-17 诱导的人星形细胞瘤细胞引起的。在我们的进一步研究中，IL-17 通过在体外和体内激活 JAK/STAT 信号通路，诱导脊髓损伤中 VEGF 的表达。此外，我们还发现，IL-17 显著改变了体内组织保存和残余尿量以及血脊髓屏障的完整性。这条新发现的 IL-17-JAK/STAT-VEGF 轴提高了我们对炎症反应期间脊髓损伤分子机制的理解，并为脊髓损伤提供了另一个潜在的靶点。
