Activation of the niacin receptor HCA2 reduces demyelination and neurofilament loss, and promotes functional recovery after spinal cord injury in mice
Activation of the niacin receptor HCA2 reduces demyelination and neurofilament loss, and promotes functional recovery after spinal cord injury in mice
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DOI：
10.1016/j.ejphar.2016.08.020
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发表时间：
2016-11-15
影响因子：
5
通讯作者：
Wang, Yuliang
中科院分区：
文献类型：
--
作者：
Yang, Ruilin;He, Jiyong;Wang, Yuliang
脊髓损伤 (SCI) 后，会出现急性期的替代活化 (M2) 巨噬细胞浸润，随后是经典活化 (M1) 巨噬细胞在伤口中积聚的长期阶段，这被认为会破坏愈合并损害器官功能。因此，能够调节巨噬细胞表型的药物可能会给 SCI 患者带来显着的益处。在本研究中，我们证明烟酸受体 HCA(2) 在 M1 巨噬细胞而非 M2 巨噬细胞的细胞表面特异性表达。用烟酸（300 μM）处理 M1 巨噬细胞会导致 p65 NF-kappa B 磷酸化下调，与 M1 标记物（包括 CD86、IL-12 和 IL-6）水平显着降低相关，而 M2 标记物（如 CD206、IL-10 和 IL-13）表达显着增加，表明烟酸导致 M1 到 M2。此外，M1-少突胶质细胞前体细胞（OPC）与烟酸共培养物的处理显着促进了髓磷脂结合蛋白（MBP）的表达。 C57/BL6 小鼠 SCI 一周后，伤口中表达 HCA(2) 受体的 M1 巨噬细胞明显积聚。用烟酸（100 mg/kg）治疗 SCI 小鼠，导致伤口中 M1 巨噬细胞数量急剧减少，而 M2 巨噬细胞数量显着增加。这与炎症的强劲消退、脱髓鞘和神经丝损失的减弱以及运动功能的显着改善有关。因此，HCA(2)受体可以作为促进SCI后恢复的治疗靶点。 (C) 2016 年由 Elsevier B.V. 出版
After spinal cord injury (SCI), there is an acute phase of alternatively activated (M2) macrophage infiltration, followed by a long-lasting phase of classically activated (M1) macrophage accumulation in the wound, which is believed to derail healing and compromize organ functions. Thus, agents which are able to modulate macrophage phenotypes may provide significant benefits to SCI patients. In the present study, we demonstrate that the niacin receptor HCA(2) is specifically expressed on the cell surface of M1 but not M2 macrophages. Treatment of M1 macrophages with niacin (300 mu M) resulted in down-regulation of the p65 NF-kappa B phosphorylation, associated with a marked decrease in the levels of M1 markers, including CD86, IL-12, and IL-6, and a significant increase in the expressions of M2 markers, such as CD206, IL-10, and IL-13, suggesting that niacin causes a shift of M1 to M2. Moreover, treatment of the M1-oligodendrocyte precursor cell (OPC) co-cultures with niacin markedly promoted the expression of myelin binding protein (MBP). After SCI in C57/BL6 mice for a week, a marked accumulation of M1 macrophages, which expressed HCA(2) receptor, was evident in the wound. Treatment of the SCI mice with niacin (100 mg/kg) resulted in a dramatic decrease in the number of M1 macrophages and a significant increase in the number of M2 macrophages in the wound. This was associated with a robust inflammation resolution, attenuation of demyelination and neurofilament loss, and significant improvement of locomotor function. Thus, HCA(2) receptor may serve as a therapeutic target to promote post-SCI recovery. (C) 2016 Published by Elsevier B.V.