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Dynorphin activation of kappa opioid receptor promotes microglial polarization toward M2 phenotype via TLR4/NF-κB

Lin Liu1, Yingtong Xu1, Hongmei Dai1

  • 11Department of Pediatrics, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, ChangshaHunan, 410013 China.

Cell & Bioscience
|March 25, 2020
PubMed
Abstract

Insights

Dynorphin, via kappa opioid receptor (KOR) activation, shifts microglia to an anti-inflammatory M2 state. This mechanism inhibits the TLR4/NF-κB pathway, offering a potential therapeutic strategy for epilepsy.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglia-driven neuroinflammation is implicated in epilepsy.
  • Modulating microglial polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) is a therapeutic target for epileptogenesis.
  • Dynorphins have previously shown epilepsy protection through kappa opioid receptor (KOR) activation.

Purpose of the Study:

  • To investigate the role of dynorphin in regulating microglial polarization.
  • To elucidate the underlying mechanism of dynorphin's action on microglia.

Main Methods:

  • Established a pilocarpine-induced rat epilepsy model.
  • Utilized lipopolysaccharide (LPS)-activated BV-2 microglial cells to model inflammation.
  • Assessed neuronal apoptosis and microglial polarization.

Main Results:

  • Overexpression of prodynorphin (PDYN) reduced neuronal apoptosis and promoted M2 microglial polarization in epileptic rats.
  • Dynorphin/KOR activation inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in LPS-stimulated microglia.
  • Dynorphin-induced M2 polarization protected primary hippocampal neurons from apoptosis.

Conclusions:

  • Dynorphin activation of KOR promotes M2 microglial polarization.
  • This polarization is achieved by inhibiting the TLR4/NF-κB pathway.
  • Dynorphin represents a potential therapeutic agent for epilepsy by modulating neuroinflammation.
Keywords:
DynorphinM1M2 polarizationMicrogliaNF-κbProdynorphinTLR4

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