MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1

Frontiers in Pharmacology

Yuchen Guo¹  Zhibing Song¹  Qian Zhang¹  Tiejun Li²  Yuefan Zhang³  Yulan Liu⁴  Yuliang Wang⁵  Junqin Mao⁶  Tamer A. Addissouky⁷  Fayed A. K. Megahed⁸  Yongsheng Yu⁸  Shanshan Deng⁸ 

[1] College of Pharmacology, Anhui University of Chinese Medicine, Hefei, China;D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China;Department of Clinical Pharmacy, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of Pharmacy, The Air Force Hospital From Eastern Theater of PLA, Nanjing, China;;Joint International Research Laboratory of Metabolic and Developmental Sciences, Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, Fudan-SJTU-Nottingham Plant Biotechnology R&MLS Ministry of Health, Alexandria, Egypt;Nucliec Acid Research Departement, Genetic Engineering and Biotechnological Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt;School of Medicine, Shanghai University, Shanghai, China;

关键词: brain ischemia;    microglia polarization;    inflammation;    monocyte locomotion inhibitory factor (MLIF);    eukaryotic translation elongation factor 1A1 (eEF1A1);   

DOI  :  10.3389/fphar.2021.725268

来源: DOAJ

【 摘 要 】

Monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide from Entamoeba histolytica. Our previous study found that MLIF protects against ischemic stroke in rats and mice and exerts a neuroprotection effect in human neuroblastoma SH-SY5Y cells. Microglia/macrophage polarization has been proven to be vital in the pathology of ischemic stroke. Nevertheless, whether MLIF is able to modulate microglia/macrophage polarization remains unclear. We performed middle cerebral artery occlusion (MCAO) on C57BL/6J male mice and induced cultured BV2 microglia by oxygen-glucose deprivation (OGD), respectively. Immunfluorescence was utilized to detect the M1/2 markers, such as CD206 and CD16/32. qPCR and ELISA were used to detect the signature gene change of M1/2. The MAPK and NF-κB pathway associated proteins were measured by Western blot. To identify the protein target of MLIF, a pull-down assay was performed. We found that MLIF promoted microglia transferring from a “sick” M1 phenotype to a “healthy” M2 phenotype in vivo or in vitro. Furthermore, we proved that eukaryotic elongation factor 1A1 (eEF1A1) was involved in the modulation of microglia/macrophage polarization. Knocking down eEF1A1 by siRNA exhibited the M1 promotion effect and M2 inhibition effect. Taken together, our results demonstrated MLIF modulated microglia/macrophage polarization by targeting eEF1A1 in ischemic stroke.

【 授权许可】

Unknown