BACKGROUND Spinal cord injury (SCI) causes devastating neurological consequences, which can result in partial or total paralysis. Irreversible neurological deficits and glial scar formation are characteristic of SCI. Inflammatory responses are a major component of secondary injury and play a central role in regulating the pathogenesis of SCI. IL-20 is a proinflammatory cytokine involved in renal fibrosis and liver cirrhosis through its role in upregulating TGF-β1 production. However, the role of IL-20 in SCI remains unclear. We hypothesize that IL-20 is upregulated after SCI and is involved in regulating the neuroinflammatory response. METHODS The expression of IL-20 and its receptors was examined in SCI rats. The regulatory roles of IL-20 in astrocytes and neuron cells were examined. The therapeutic effects of anti-IL-20 monoclonal antibody (mAb) 7E in SCI rats were evaluated. RESULTS Immunofluorescence staining showed that IL-20 and its receptors were expressed in astrocytes, oligodendrocytes, and microglia in the spinal cord after SCI in rats. In vitro, IL-20 enhanced astrocyte reactivation and cell migration in human astrocyte (HA) cells by upregulating glial fibrillary acidic protein (GFAP), TGF-β1, TNF-α, MCP-1, and IL-6 expression. IL-20 inhibited cell proliferation and nerve growth factor (NGF)-derived neurite outgrowth in PC-12 cells through Sema3A/NRP-1 upregulation. In vivo, treating SCI rats with anti-IL-20 mAb 7E remarkably inhibited the inflammatory responses. 7E treatment not only improved motor and sensory functions but also improved spinal cord tissue preservation and reduced glial scar formation in SCI rats. CONCLUSIONS IL-20 might regulate astrocyte reactivation and axonal regeneration and result in the secondary injury in SCI. These findings demonstrated that IL-20 may be a promising target for SCI treatment.

中文翻译：

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抗IL-20抗体可改善大鼠脊髓损伤后的运动功能并减少神经胶质疤痕的形成。

背景技术脊髓损伤（SCI）引起毁灭性的神经系统后果，其可导致部分或全部瘫痪。不可逆的神经功能缺损和神经胶质瘢痕形成是SCI的特征。炎症反应是继发性损伤的主要组成部分，在调节SCI的发病机理中起着核心作用。IL-20是一种促炎性细胞因子，通过上调TGF-β1的产生而参与肾脏纤维化和肝硬化。但是，IL-20在SCI中的作用仍不清楚。我们假设IL-20在SCI后被上调，并参与调节神经炎症反应。方法检测SCI大鼠IL-20及其受体的表达。检查了IL-20在星形胶质细胞和神经元细胞中的调节作用。评估了抗IL-20单克隆抗体（mAb）7E在SCI大鼠中的治疗作用。结果免疫荧光染色显示，SCI后脊髓中的星形胶质细胞，少突胶质细胞和小胶质细胞中均表达IL-20及其受体。在体外，IL-20通过上调神经胶质纤维酸性蛋白（GFAP），TGF-β1，TNF-α，MCP-1和IL-6的表达来增强人类星形胶质细胞（HA）细胞中星形胶质细胞的活化和细胞迁移。IL-20通过Sema3A / NRP-1上调抑制PC-12细胞的细胞增殖和神经生长因子（NGF）衍生的神经突生长。在体内，用抗IL-20 mAb 7E治疗SCI大鼠可明显抑制炎症反应。7E治疗不仅改善了运动和感觉功能，而且改善了脊髓损伤大鼠的脊髓组织保存能力并减少了胶质瘢痕形成。结论IL-20可能调节星形胶质细胞的活化和轴突再生，并导致SCI继发性损伤。这些发现证明IL-20可能是SCI治疗的有希望的靶标。