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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8452963 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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