Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2

Yeqi Li1, Cui Yin2, Jinhong Jiang2

  • 1School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Insights

Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) regulates microglial activation and glucose metabolism in neuropathic pain. This protein suppresses inflammation and promotes healing, offering a potential therapeutic target for pain relief.

Area of Science:

  • Neuroscience
  • Immunology
  • Metabolic Research

Background:

  • Microglia are key players in neuroinflammation and are implicated in neuropathic pain.
  • Glucose metabolic programming influences microglial activation states and functions.
  • Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) is involved in anti-inflammatory responses.

Purpose of the Study:

  • To investigate the role of TNFAIP8L2 in microglial activation and its relationship with glucose metabolic reprogramming in neuropathic pain.
  • To elucidate the mechanism by which TNFAIP8L2 influences microglial phenotypes.

Main Methods:

  • In vitro studies using BV2 microglial cells stimulated with LPS/IFNγ or IL-4 to induce distinct microglial phenotypes.
  • In vivo experiments involving chronic constriction injury (CCI) of the sciatic nerve in a neuropathic pain model.
  • Analysis of glucose metabolism, including glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), and signaling pathways (MAPK/mTOR/HIF-1α).

Main Results:

  • TNFAIP8L2 was found to decrease glycolysis and enhance mitochondrial OXPHOS in inflammatory microglia in vitro.
  • Blocking the glycolytic pathway abrogated TNFAIP8L2-mediated microglial activation.
  • TNFAIP8L2 suppressed inflammatory microglial activation and promoted restorative activation in both cell cultures and in vivo models of neuropathic pain.
  • TNFAIP8L2 regulates microglial activation and glucose metabolism via the MAPK/mTOR/HIF-1α signaling axis.

Conclusions:

  • TNFAIP8L2 plays a critical role in modulating microglial phenotypes and glucose metabolism during neuropathic pain.
  • The findings provide insights into the interplay between metabolic reprogramming and microglial phenotypic transition.
  • TNFAIP8L2 represents a potential therapeutic target for the prevention and treatment of neuropathic pain.