Lipopolysaccharide and Curcumin Co-Stimulation Potentiates Olfactory Ensheathing Cell Phagocytosis Via Enhancing Their Activation
Lipopolysaccharide and Curcumin Co-Stimulation Potentiates Olfactory Ensheathing Cell Phagocytosis Via Enhancing Their Activation
复制标题
脂多糖和姜黄素共同刺激通过增强嗅鞘细胞的激活来增强其吞噬作用
DOI：
10.1007/s13311-016-0485-8
复制
发表时间：
2017-04-01
影响因子：
5.7
通讯作者：
Yang, Hao
中科院分区：
文献类型：
--
作者：
Hao, Ding-Jun;Liu, Cuicui;Yang, Hao
中枢神经系统（CNS）损伤或神经退行性疾病后的逐渐恶化通常伴随着退化和凋亡的神经组织碎片的浸润。快速有效地清除这些变质的细胞产物对于创造一个允许这些受损神经元再生的环境至关重要。我们最近的报告显示，嗅鞘细胞（OECs）的吞噬活性可以在这种恶劣的环境中对神经元的生长做出实质性的贡献。然而，关于如何进一步提高oec吞噬有害产物的能力，人们知之甚少。本研究采用体外原代细胞模型，探讨脂多糖（LPS）和姜黄素（CCM）共同刺激对oec吞噬活性的影响及其可能的机制。我们的研究结果表明，与正常和LPS或CCM处理的OEC相比，LPS和CCM共同刺激OEC可以显著增强OEC的活化，显示出趋化因子（C-X-C基序）配体1、趋化因子（C-X-C基序）配体2、肿瘤坏死因子-α和toll样受体4的显著上调，增加OEC的增殖活性，提高吞噬能力。更重要的是，这种增强的吞噬活性极大地促进了神经元在不良培养条件下的生长。此外，在LPS和CCM共同刺激激活的oec中，转谷氨酰胺酶-2和磷脂酰丝氨酸受体的上调可能是观察到的细胞事件的机制，因为胱胺（转谷氨酰胺酶-2的特异性抑制剂）和中性粒细胞弹性酶（磷脂酰丝氨酸受体的裂解酶）可以有效地消除oec的所有积极作用，包括吞噬能力和促进神经元生长的作用。本研究为oec与LPS、CCM联合应用修复外伤性神经损伤和神经系统疾病提供了一种替代策略。
The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment. However, little is known about how to further increase the ability of OECs in phagocytosing deleterious products. Here, we used an in vitro model of primary cells to investigate the effects of lipopolysaccharide (LPS) and curcumin (CCM) co-stimulation on phagocytic activity of OECs and the possible underlying mechanisms. Our results showed that co-stimulation using LPS and CCM can significantly enhance the activation of OECs, displaying a remarkable up-regulation in chemokine (C-X-C motif) ligand 1, chemokine (C-X-C motif) ligand 2, tumor necrosis factor-α, and Toll-like receptor 4, increased OEC proliferative activity, and improved phagocytic capacity compared with normal and LPS- or CCM-treated OECs. More importantly, this potentiated phagocytosis activity greatly facilitated neuronal growth under hostile culture conditions. Moreover, the up-regulation of transglutaminase-2 and phosphatidylserine receptor in OECs activated by LPS and CCM co-stimulation are likely responsible for mechanisms underlying the observed cellular events, because cystamine (a specific inhibitor of transglutaminase-2) and neutrophil elastase (a cleavage enzyme of phosphatidylserine receptor) can effectively abrogate all the positive effects of OECs, including phagocytic capacity and promotive effects on neuronal growth. This study provides an alternative strategy for the repair of traumatic nerve injury and neurologic diseases with the application of OECs in combination with LPS and CCM.