Research Paper Volume 11, Issue 3 pp 898—907
p38MAPK/SGK1 signaling regulates macrophage polarization in experimental autoimmune encephalomyelitis
- 1 Department of Neurology, Bethune International Peace Hospital, Shijiazhuang 050000, China
- 2 Dynacare, Ottawa, Ontario K1L8H2, Canada
- 3 Department of Neurology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
- 4 Key Laboratory of Hebei Neurology, Shijiazhuang 050000, China
- 5 Laboratory Medicine Center of Qilu Hospital of Shandong University (Qingdao), Qingdao 266035, China
received: December 19, 2018 ; accepted: January 15, 2019 ; published: February 4, 2019 ;https://doi.org/10.18632/aging.101786
How to Cite
Copyright: Li et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Multiple sclerosis (MS) is characterized with multifocal demyelination resulting from activation and infiltration of inflammatory cells into the central nerve system. Recent reports suggest that p38 mitogen-activated protein kinase (MAPK) / serum- and glucocorticoid-inducible protein kinase 1 (SGK1) signaling pathway contributes to the pathology of MS through regulation of immunity. However, the role of this signaling pathway in MS-related macrophage activation and polarization has not been studied. Here, we used an experimental autoimmune encephalomyelitis (EAE) model for MS to study the role of p38MAPK/SGK1 signaling in the macrophage polarization and its effects on the development and severity of EAE. Here, we found that p38MAPK/SGK1 signaling is required for IL4-induced M2 macrophage polarization in vitro. Chitin-induced M2 macrophage polarization reduces the severity of EAE in mice. Generation of an adeno-associated virus (AAV) carrying sh-p38 or sh-SGK1 under the control of a CD68 promoter successfully knockdown p38 or SGK1 levels in vitro and in vivo. Treatment with AAV-sh-p38 or AAV-sh-SGK1 abolished the effects of Chitin on macrophage polarization and the severity of EAE. Thus, our data suggest that p38MAPK/SGK1 signaling induces M2 macrophage polarization, which reduces the severity of EAE, a model for MS.