Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy.
Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy.
Cytokine. 2020 Jan;125:154777. doi: 10.1016/j.cyto.2019.154777. Epub 2019 Aug 7.
Literature studies suggest important protective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on inflammatory pathways affecting joint and cerebral diseases. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. Therefore the aim of this study was to identify the molecular targets of PEMFs anti-neuroinflammatory action. The effects of PEMF exposure in cytokine production by lipopolysaccharide (LPS)-activated N9 microglial cells as well as the pathways involved, including adenylyl cyclase (AC), phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and delta (PKC-δ), p38, ERK1/2, JNK1/2 mitogen activated protein kinases (MAPK), Akt and caspase 1, were investigated. In addition, the ability of PEMFs to modulate ROS generation, cell invasion and phagocytosis, was addressed. PEMFs reduced the LPS-increased production of TNF-α and IL-1β in N9 cells, through a pathway involving JNK1/2. Furthermore, they decreased the LPS-induced release of IL-6, by a mechanism not dependent on AC, PLC, PKC-ε, PKC-δ, p38, ERK1/2, JNK1/2, Akt and caspase 1. Importantly, a significant effect of PEMFs in the reduction of crucial cell functions specific of microglia like ROS generation, cell invasion and phagocytosis was found. PEMFs inhibit neuroinflammation in N9 cells through a mechanism involving, at least in part, the activation of JNK MAPK signalling pathway and may be relevant to treat a variety of diseases characterized by neuroinflammation.
文献研究表明，低频低能量脉冲电磁场（PEMFs）对影响关节和脑部疾病的炎症途径具有重要的保护作用。然而，目前尚不清楚它们是基于何种机制影响神经保护作用的，其具体机制尚不清楚。因此，本研究旨在确定 PEMF 抗神经炎症作用的分子靶点。研究了 PEMF 暴露对脂多糖（LPS）激活的 N9 小胶质细胞细胞因子产生的影响及其涉及的途径，包括腺苷酸环化酶（AC）、磷脂酶 C（PLC）、蛋白激酶 C ɛ（PKC-ɛ）和 δ（PKC-δ）、p38、细胞外信号调节激酶 1/2（ERK1/2）、c-Jun N 端激酶 1/2（JNK1/2）丝裂原激活蛋白激酶（MAPK）、Akt 和半胱天冬酶 1。此外，还研究了 PEMFs 调节活性氧（ROS）生成、细胞侵袭和吞噬作用的能力。PEMFs 通过 JNK1/2 途径降低 LPS 增加的 N9 细胞中 TNF-α和 IL-1β的产生。此外，它们通过不依赖于 AC、PLC、PKC-ɛ、PKC-δ、p38、ERK1/2、JNK1/2、Akt 和半胱天冬酶 1 的机制降低 LPS 诱导的 IL-6 释放。重要的是，发现 PEMFs 对减少小胶质细胞特定细胞功能（如 ROS 生成、细胞侵袭和吞噬作用）具有显著作用。PEMFs 通过至少部分激活 JNK MAPK 信号通路抑制 N9 细胞中的神经炎症，可能与治疗多种以神经炎症为特征的疾病有关。
