An ανI23 Integrin-Binding Peptide Ameliorates Symptoms of Chronic Progressive Experimental Autoimmune Encephalomyelitis by Alleviating Neuroinflammatory Responses in Mice
An ανI23 Integrin-Binding Peptide Ameliorates Symptoms of Chronic Progressive Experimental Autoimmune Encephalomyelitis by Alleviating Neuroinflammatory Responses in Mice
复制标题
αββ3 整合素结合肽通过减轻小鼠的神经炎症反应来改善慢性进行性实验性自身免疫性脑脊髓炎的症状
DOI：
10.1007/s11481-014-9532-6
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发表时间：
2014-06-01
影响因子：
6.2
通讯作者：
Han, Shu
中科院分区：
文献类型：
--
作者：
Zhang, Fan;Yang, Jing;Han, Shu
MOG 35 -55在C57 BL/6小鼠中触发慢性、进行性实验性自身免疫性脑脊髓炎（EAE），并且该模型中EAE的临床过程的特征在于巨噬细胞浸润、轴突脱髓鞘/损伤和进行性瘫痪。这些阶段通常与中枢神经系统（CNS）中的炎症反应有关。本研究旨在研究C16的作用，C16是一种ανβ3整联蛋白结合肽，其靶向参与外渗炎性细胞的跨内皮迁移的整联蛋白。C16仅应用2周，但这种疗法的益处持续至少8周。采用多种组织学和免疫组织化学染色研究、蛋白质印迹法、酶联免疫吸附试验、电子显微镜和皮层体感诱发电位（c-SEP）电生理测试来评估不同治疗的EAE模型小鼠的炎症程度、轴突损失、白色物质脱髓鞘、神经元凋亡、胶质增生程度、促炎细胞因子表达和功能恢复。结果表明，C16可抑制EAE大鼠外周血白细胞和巨噬细胞的聚集和浸润，减少促炎细胞因子（肿瘤坏死因子-α和干扰素-γ）的表达，从而减轻和延缓EAE的进展。此外，星形胶质细胞增生，脱髓鞘，轴突和神经元的损失都减轻C16治疗的EAE动物，有助于改善功能。这些数据表明，C16肽可以作为一种保护剂，减少神经炎症反应和改善微环境。
MOG35-55 triggers chronic, progressive experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, and the clinical course of EAE in this model is characterized by macrophage infiltration, axonal demyelination/damage, and progressive paralysis. These stages are usually associated with inflammatory responses in the central nervous system (CNS). This study was designed to investigate the effects of C16, an ανβ3 integrin-binding peptide that targets integrins involved in the transendothelial migration of extravasating inflammatory cells. C16 was applied for only 2 weeks, but the benefits of this therapy lasted at least 8 weeks. Multiple histological and immunohistochemical staining studies, western blotting, enzyme-linked immunosorbent assays, electron microscopy, and cortical somatosensory-evoked potential (c-SEP) electrophysiological tests were employed to assess the degree of inflammation, axonal loss, white matter demyelination, neuronal apoptosis, extent of gliosis, expression of pro-inflammatory cytokines, and functional recovery of differently treated EAE model mice. The results showed that C16 treatment inhibited extensive leukocyte and macrophage accumulation and infiltration, reduced the expression of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-γ), and thereby attenuated and delayed the progression of EAE. Moreover, astrogliosis, demyelination, and axonal and neuronal loss were all alleviated in C16-treated EAE animals, contributing to the improvement of function. These data suggest that the C16 peptide may act as a protective agent by reducing neuroinflammatory responses and improving the microenvironment.