PMID- 37573838
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20230823
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 65
DP  - 2023 Sep
TI  - Methylglyoxal suppresses microglia inflammatory response through NRF2-IkappaBzeta 
      pathway.
PG  - 102843
LID - S2213-2317(23)00244-6 [pii]
LID - 10.1016/j.redox.2023.102843 [doi]
LID - 102843
AB  - Methylglyoxal (MGO) is a highly reactive metabolite generated by glycolysis. 
      Although abnormal accumulation of MGO has been reported in several autoimmune 
      diseases such as multiple sclerosis and rheumatoid arthritis, the role of MGO in 
      autoimmune diseases has not yet been fully investigated. In this study, we found 
      that the intracellular MGO levels increased in activated immune cells, such as 
      microglia and lymphocytes. Treatment with MGO inhibited inflammatory cell 
      accumulation in the spinal cord and ameliorated the clinical symptoms in EAE 
      mice. Further analysis indicated that MGO suppressed M1-polarization of microglia 
      cells and diminished their inflammatory cytokine production. MGO also inhibited 
      the ability of microglial cells to recruit and activate lymphocytes by decreasing 
      chemokine secretion and expression of co-stimulatory molecules. Furthermore, MGO 
      negatively regulated glycolysis by suppressing glucose transporter 1 expression. 
      Mechanically, we found that MGO could activate nuclear factor erythroid 2-related 
      factor 2 (NRF2) pathway and NRF2 could bind to the promoter of IkappaBzeta gene and 
      suppressed its transcription and subsequently pro-inflammatory cytokine 
      production. In conclusion, our results showed that MGO acts as an 
      immunosuppressive metabolite by activating the NRF2-IkappaBzeta.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Wei, Shu-Li
AU  - Wei SL
AD  - Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan 250011, PR China.
FAU - Yang, Ying
AU  - Yang Y
AD  - Department of Pharmacy, The Affiliated Hospital of Shandong University of 
      Traditional Chinese Medicine, Jinan, 250014, China.
FAU - Si, Wei-Yue
AU  - Si WY
AD  - Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan 250011, PR China.
FAU - Zhou, Yang
AU  - Zhou Y
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China.
FAU - Du, Tong
AU  - Du T
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China; Shandong Institute of Neuroimmunology, Jinan 
      250014, PR China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China; Shandong Institute of Neuroimmunology, Jinan 
      250014, PR China.
FAU - Li, Xiao-Li
AU  - Li XL
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China; Shandong Institute of Neuroimmunology, Jinan 
      250014, PR China.
FAU - Duan, Ruo-Nan
AU  - Duan RN
AD  - Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong 
      University, Jinan, Shandong, 250012, China.
FAU - Duan, Rui-Sheng
AU  - Duan RS
AD  - Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan 250011, PR China; Department of Neurology, The First Affiliated 
      Hospital of Shandong First Medical University, Jinan 250014, PR China; Shandong 
      Institute of Neuroimmunology, Jinan 250014, PR China. Electronic address: 
      ruisheng_duan@163.com.
FAU - Yang, Chun-Lin
AU  - Yang CL
AD  - Department of Neurology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan 250014, PR China; Shandong Institute of Neuroimmunology, Jinan 
      250014, PR China. Electronic address: muyilin1991@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230808
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (NF-E2-Related Factor 2)
RN  - 722KLD7415 (Pyruvaldehyde)
RN  - 3A3U0GI71G (Magnesium Oxide)
RN  - 0 (Cytokines)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Microglia/metabolism
MH  - *Encephalomyelitis, Autoimmune, Experimental/genetics/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Pyruvaldehyde/metabolism
MH  - Magnesium Oxide/metabolism
MH  - Mice, Inbred C57BL
MH  - Cytokines/metabolism
PMC - PMC10440576
OTO - NOTNLM
OT  - Experimental autoimmune encephalomyelitis (EAE)
OT  - Methylglyoxal
OT  - Microglia
OT  - Nuclear factor erythroid 2-related factor 2 (NRF2)
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/14 00:42
MHDA- 2023/08/21 06:42
PMCR- 2023/08/08
CRDT- 2023/08/13 18:40
PHST- 2023/07/07 00:00 [received]
PHST- 2023/08/05 00:00 [revised]
PHST- 2023/08/06 00:00 [accepted]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/08/14 00:42 [pubmed]
PHST- 2023/08/13 18:40 [entrez]
PHST- 2023/08/08 00:00 [pmc-release]
AID - S2213-2317(23)00244-6 [pii]
AID - 102843 [pii]
AID - 10.1016/j.redox.2023.102843 [doi]
PST - ppublish
SO  - Redox Biol. 2023 Sep;65:102843. doi: 10.1016/j.redox.2023.102843. Epub 2023 Aug 
      8.