Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain
Copyright © 2024 Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:169 |
|---|---|
| Enthalten in: |
The international journal of biochemistry & cell biology - 169(2024) vom: 21. März, Seite 106541 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Yeqi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Carrier Proteins |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.biocel.2024.106541 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367991284 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367991284 | ||
| 003 | DE-627 | ||
| 005 | 20240325234753.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240204s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.biocel.2024.106541 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1346.xml |
| 035 | |a (DE-627)NLM367991284 | ||
| 035 | |a (NLM)38309648 | ||
| 035 | |a (PII)S1357-2725(24)00032-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Yeqi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HIF-1α | |
| 650 | 4 | |a Metabolic reprogramming | |
| 650 | 4 | |a Microglia | |
| 650 | 4 | |a Neuropathic pain | |
| 650 | 4 | |a TNFAIP8L2 | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 700 | 1 | |a Yin, Cui |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jinhong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Feifei |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Yanhong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wuyang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The international journal of biochemistry & cell biology |d 1996 |g 169(2024) vom: 21. März, Seite 106541 |w (DE-627)NLM074736698 |x 1878-5875 |7 nnns |
| 773 | 1 | 8 | |g volume:169 |g year:2024 |g day:21 |g month:03 |g pages:106541 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.biocel.2024.106541 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 169 |j 2024 |b 21 |c 03 |h 106541 | ||