PMID- 36615301
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230111
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 28
IP  - 1
DP  - 2022 Dec 23
TI  - Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of 
      Thioredoxin Reductase 1 in RAW 264.7 Cells.
LID - 10.3390/molecules28010107 [doi]
LID - 107
AB  - Macrophages secrete a variety of pro-inflammatory cytokines in response to 
      pathogen-associated molecular patterns (PAMPs) and damage-associated molecular 
      patterns (DAMPs) but abnormal release of cytokines unfortunately promotes 
      cytokine storms. Dimethyl fumarate (DMF), an FDA-approved drug for multiple 
      sclerosis (MS) treatment, has been found as an effective therapeutic agent for 
      resolution. In this study, the anti-inflammatory effect of DMF was found to 
      correlate to selenoprotein thioredoxin reductase 1 (TXNRD1). DMF irreversibly 
      modified the Sec(498) residue and C-terminal catalytic cysteine residues of 
      TXNRD1 in a time- and dose-dependent manner. In LPS-stimulated RAW 264.7 cells, 
      cellular TXNRD activity was increased through up-regulation of the protein level 
      and DMF inhibited TXNRD activity and the nitric oxide (NO) production of RAW 
      264.7 cells. Meanwhile, the inhibition of TXNRD1 by DMF would contribute to the 
      redox regulation of inflammation and promote the nuclear factor erythroid 
      2-related factor 2 (NRF2) activation. Notably, inhibition of cellular TXNRD1 by 
      auranofin or TRi-1 showed anti-inflammatory effect in RAW 264.7 cells. This 
      finding demonstrated that targeting TXNRD1 is a potential mechanism of using 
      immunometabolites for dousing inflammation in response to pathogens and 
      highlights the potential of TXNRD1 inhibitors in immune regulation.
FAU - Yang, Rui
AU  - Yang R
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Sun, Shibo
AU  - Sun S
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Guo, Yining
AU  - Guo Y
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Meng, Yao
AU  - Meng Y
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Liu, Haowen
AU  - Liu H
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Shi, Meiyun
AU  - Shi M
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
FAU - Guan, Shui
AU  - Guan S
AUID- ORCID: 0000-0001-7617-8081
AD  - State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and 
      Tissue Engineering, School of Chemical Engineering, Dalian University of 
      Technology, Dalian 116023, China.
AD  - Research & Educational Center for the Control Engineering of Translational 
      Precision Medicine, School of Biomedical Engineering, Dalian University of 
      Technology, Dalian 116024, China.
FAU - Xu, Jianqiang
AU  - Xu J
AUID- ORCID: 0000-0002-1289-5943
AD  - School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial 
      Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and 
      Separation, Dalian University of Technology, Panjin 124221, China.
LA  - eng
GR  - 31670767/National Natural Science Foundation of China/
GR  - DUT20LK36/Fundamental Research Funds for the Central Universities/
GR  - ZJKF2004/Liaoning Key Laboratory of Chemical Additive Synthesis and Separation/
PT  - Journal Article
DEP - 20221223
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - FO2303MNI2 (Dimethyl Fumarate)
RN  - EC 1.8.1.9 (Thioredoxin Reductase 1)
RN  - 0 (Cytokines)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Dimethyl Fumarate/pharmacology/chemistry
MH  - *Thioredoxin Reductase 1/metabolism
MH  - RAW 264.7 Cells
MH  - Inflammation/drug therapy
MH  - Cytokines
MH  - Anti-Inflammatory Agents/pharmacology
MH  - NF-E2-Related Factor 2/metabolism
PMC - PMC9822326
OTO - NOTNLM
OT  - anti-inflammation
OT  - dimethyl fumarate
OT  - immunometabolite
OT  - redox regulation
OT  - selenoprotein
OT  - thioredoxin reductase (TXNRD)
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/11 06:00
PMCR- 2022/12/23
CRDT- 2023/01/08 01:33
PHST- 2022/11/30 00:00 [received]
PHST- 2022/12/18 00:00 [revised]
PHST- 2022/12/20 00:00 [accepted]
PHST- 2023/01/08 01:33 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2022/12/23 00:00 [pmc-release]
AID - molecules28010107 [pii]
AID - molecules-28-00107 [pii]
AID - 10.3390/molecules28010107 [doi]
PST - epublish
SO  - Molecules. 2022 Dec 23;28(1):107. doi: 10.3390/molecules28010107.