2. Academic Validation
  3. Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain

Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain

  • Int J Biochem Cell Biol. 2024 Feb 1:169:106541. doi: 10.1016/j.biocel.2024.106541.
Yeqi Li 1,  Cui Yin 2,  Jinhong Jiang 2,  Huan Yang 1,  Feifei Zhang 2,  Yanhong Xing 2,  Wuyang Wang 3,  Chen Lu 4
Affiliations

Affiliations

  • 1 School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected].
  • 4 School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected].
PMID: 38309648 DOI: 10.1016/j.biocel.2024.106541
Abstract

Microglial are major players in neuroinflammation that have recently emerged as potential therapeutic targets for neuropathic pain. Glucose metabolic programming has been linked to differential activation state and function in microglia. Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) is an important component in regulating the anti-inflammatory response. However, the role of TNFAIP8L2 in microglia differential state during neuropathic pain and its interplay with glucose metabolic reprogramming in microglia has not yet been determined. Thus, we aimed to investigate the role of TNFAIP8L2 in the status of microglia in vitro and in vivo. BV2 microglial cells were treated with lipopolysaccharides plus interferon-gamma (LPS/IFNγ) or interleukin-4 (IL-4) to induce the two different phenotypes of microglia in vitro. In vivo experiments were conducted by chronic constriction injury of the sciatic nerve (CCI). We investigated whether TNFAIP8L2 regulates glucose metabolic programming in BV2 microglial cells. The data in vitro showed that TNFAIP8L2 lowers glycolysis and increases mitochondrial oxidative phosphorylation (OXPHOS) in inflammatory microglia. Blockade of glycolytic pathway abolished TNFAIP8L2-mediated differential activation of microglia. TNFAIP8L2 suppresses inflammatory microglial activation and promotes restorative microglial activation in BV2 microglial cells and in spinal cord microglia after neuropathic pain. Furthermore, TNFAIP8L2 controls differential activation of microglia and glucose metabolic reprogramming through the MAPK/mTOR/HIF-1α signaling axis. This study reveals that TNFAIP8L2 plays a critical role in neuropathic pain, providing important insights into glucose metabolic reprogramming and microglial phenotypic transition, which indicates that TNFAIP8L2 may be used as a potential drug target for the prevention of neuropathic pain.

Keywords

HIF-1α; Metabolic reprogramming; Microglia; Neuropathic pain; TNFAIP8L2.

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