title: Activation of the niacin receptor HCA2reduces demyelination and neurofilament loss, and promotes functional recovery after spinal cord injury in mice.
abstract: 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 HCA2is specifically expressed on the cell surface of M1 but not M2 macrophages. Treatment of M1 macrophages with niacin (300μM) 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 HCA2receptor, was evident in the wound. Treatment of the SCI mice with niacin (100mg/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, HCA2receptor may serve as a therapeutic target to promote post-SCI recovery.
authors: Department of Neurosurgery, Changan Hospital, Xian, China. Electronic address: 2940464735@qq.com.
authors: Ruilin
authors: R
authors: Yang
authors: Department of Massage Rehibilitation, Changan Hospital, Xian, China. Electronic address: 623252835@qq.com.
authors: Jiyong
authors: J
authors: He
authors: Department of Orthopedics, Changan Hospital, Xian, China. Electronic address: yuliangwang75@163.com.
authors: Yuliang
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003711:Demyelinating Diseases / Q000150:complications*; D015536:Down-Regulation / Q000187:drug effects; D007382:Intermediate Filaments / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009525:Niacin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D016328:NF-kappa B; D011978:Receptors, Nicotinic; D009525:Niacin
keywords: HCA(2) receptor; Inflammation; Macrophages; Niacin; Spinal cord injury