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MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1

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...

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Autores principales: Liu, Yulan, Deng, Shanshan, Song, Zhibing, Zhang, Qian, Guo, Yuchen, Yu, Yongsheng, Wang, Yuliang, Li, Tiejun, Megahed, Fayed A. K., Addissouky, Tamer A., Mao, Junqin, Zhang, Yuefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452963/
https://www.ncbi.nlm.nih.gov/pubmed/34557098
http://dx.doi.org/10.3389/fphar.2021.725268
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author Liu, Yulan
Deng, Shanshan
Song, Zhibing
Zhang, Qian
Guo, Yuchen
Yu, Yongsheng
Wang, Yuliang
Li, Tiejun
Megahed, Fayed A. K.
Addissouky, Tamer A.
Mao, Junqin
Zhang, Yuefan
author_facet Liu, Yulan
Deng, Shanshan
Song, Zhibing
Zhang, Qian
Guo, Yuchen
Yu, Yongsheng
Wang, Yuliang
Li, Tiejun
Megahed, Fayed A. K.
Addissouky, Tamer A.
Mao, Junqin
Zhang, Yuefan
author_sort Liu, Yulan
collection PubMed
description 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.
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spelling pubmed-84529632021-09-22 MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1 Liu, Yulan Deng, Shanshan Song, Zhibing Zhang, Qian Guo, Yuchen Yu, Yongsheng Wang, Yuliang Li, Tiejun Megahed, Fayed A. K. Addissouky, Tamer A. Mao, Junqin Zhang, Yuefan Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-09-07 /pmc/articles/PMC8452963/ /pubmed/34557098 http://dx.doi.org/10.3389/fphar.2021.725268 Text en Copyright © 2021 Liu, Deng, Song, Zhang, Guo, Yu, Wang, Li, Megahed, Addissouky, Mao and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Yulan
Deng, Shanshan
Song, Zhibing
Zhang, Qian
Guo, Yuchen
Yu, Yongsheng
Wang, Yuliang
Li, Tiejun
Megahed, Fayed A. K.
Addissouky, Tamer A.
Mao, Junqin
Zhang, Yuefan
MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title_full MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title_fullStr MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title_full_unstemmed MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title_short MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1
title_sort mlif modulates microglia polarization in ischemic stroke by targeting eef1a1
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452963/
https://www.ncbi.nlm.nih.gov/pubmed/34557098
http://dx.doi.org/10.3389/fphar.2021.725268
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