Signaling pathways involved in anti-inflammatory effects of Pulsed Electromagnetic Field in microglial cells.

Author: Merighi S1, Gessi S2, Bencivenni S1, Battistello E1, Vincenzi F1, Setti S3, Cadossi M3, Borea PA1, Cadossi R3, Varani K4
Author Information:
1Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy.
2Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy. Electronic address:
3Igea Biophysics Laboratory, Carpi, Italy.
4Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy; Center for Studies on Gender Medicine, University of Ferrara, Ferrara 44121, Italy.
Conference/Journal: Cytokine.
Date published: 2019 Aug 7
Other: Volume ID: 125 , Pages: 154777 , Special Notes: doi: 10.1016/j.cyto.2019.154777. [Epub ahead of print] , Word Count: 238

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.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Inflammation; Microglia; Pulsed electromagnetic fields; Signal transduction

PMID: 31400640 DOI: 10.1016/j.cyto.2019.154777