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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• 作者：Ruilin Yang^a ; ^{2940464735@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Jiyong He^b ; ^{623252835@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yuliang Wang^c ; ^{yuliangwang75@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Niacin ; HCA2 receptor ; Spinal cord injury ; Inflammation ; Macrophages
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：124-136
• 全文大小：3597 K

文摘

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 HCA₂ is specifically expressed on the cell surface of M1 but not M2 macrophages. Treatment of M1 macrophages with niacin (300 μM) resulted in down-regulation of the p65 NF-κB 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 HCA₂ 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, HCA₂ receptor may serve as a therapeutic target to promote post-SCI recovery.