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MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1.

Yulan Liu1,2, Shanshan Deng1, Zhibing Song3

  • 1School of Medicine, Shanghai University, Shanghai, China.

Frontiers in Pharmacology
|September 24, 2021
PubMed
Summary

Monocyte locomotion inhibitory factor (MLIF) shifts microglia from a pro-inflammatory M1 to a protective M2 state. This neuroprotective effect in ischemic stroke involves targeting eukaryotic elongation factor 1A1 (eEF1A1).

Keywords:
brain ischemiaeukaryotic translation elongation factor 1A1 (eEF1A1)inflammationmicroglia polarizationmonocyte locomotion inhibitory factor (MLIF)

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Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Microglia/macrophage polarization is critical in ischemic stroke pathology.
  • Monocyte locomotion inhibitory factor (MLIF) shows neuroprotective effects against ischemic stroke.
  • The role of MLIF in modulating microglia/macrophage polarization is not well understood.

Purpose of the Study:

  • To investigate MLIF's effect on microglia/macrophage polarization in ischemic stroke.
  • To identify the molecular mechanisms and protein targets underlying MLIF's action.

Main Methods:

  • Middle cerebral artery occlusion (MCAO) model in mice and oxygen-glucose deprivation (OGD) in BV2 microglia.
  • Immunofluorescence for M1/M2 markers (CD206, CD16/32).
  • Quantitative PCR (qPCR), ELISA, Western blot, and pull-down assays to analyze gene/protein expression and interactions.

Main Results:

  • MLIF promoted the M1 to M2 phenotype shift in microglia both *in vivo* and *in vitro*.
  • Eukaryotic elongation factor 1A1 (eEF1A1) was identified as a key mediator in MLIF's polarization modulation.
  • siRNA-mediated knockdown of eEF1A1 reversed the beneficial M2 shift, promoting M1 and inhibiting M2 phenotypes.

Conclusions:

  • MLIF effectively modulates microglia/macrophage polarization towards a protective M2 phenotype in ischemic stroke.
  • The mechanism involves MLIF targeting eEF1A1, influencing the M1/M2 balance.
  • This finding highlights MLIF as a potential therapeutic agent for ischemic stroke via immune modulation.