PMID- 32768653
OWN - NLM
STAT- MEDLINE
DCOM- 20201102
LR  - 20201102
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 333
DP  - 2020 Oct 15
TI  - Methamphetamine induced neuroinflammation in mouse brain and microglial cell line 
      BV2: Roles of the TLR4/TRIF/Peli1 signaling axis.
PG  - 150-158
LID - S0378-4274(20)30346-5 [pii]
LID - 10.1016/j.toxlet.2020.07.028 [doi]
AB  - Methamphetamine (Meth), a highly addictive drug, can induce irreversible neuronal 
      damage and cause neuropsychiatric and cognitive disorders. Meth's effects on 
      modulating microglial neuroimmune functions and eliciting neuroinflammation have 
      attracted considerable attention in recent years. Recent evident of the effect of 
      the non-dependent domain containing adaptor inducing interferon (TRIF)/Pellino1 
      (Peli1) signaling axis on pro-inflammatory cytokine production provides novel 
      clues for inflammation. Therefore, our study investigated Meth-induced 
      neurotoxicity from a neuropathological perspective by examining TLR4-TRIF-Peli1 
      axis signaling activation. Meth significantly activated microglia accompanied by 
      marked increase of TLR4 and TRIF expression, NF-kB and MAPK pathways activation 
      and the production of IL-1beta, TNF-alpha and IL-6. Peli1 was involved in Meth-mediated 
      neuroinflammation and knockdown of Peli1 strongly reversed NF-kB and MAPK 
      pathways activation and pro-inflammatory cytokine excretion. Intriguingly, Peli1 
      upregulation induced by Meth was dependent on TRIF rather than the myloid 
      differentiation factor 88 (MyD88) pathway, since the silencing of TRIF 
      significantly suppressed Meth-induced Peli1 upregulation, while MyD88 knockdown 
      had no obvious impact. Additionally, an in vivo study verified TLR4-TRIF-Peli1 
      axis activation and an enhanced level of downstream cytokine expression in the 
      cortex after Meth treatment. Therefore, these findings provide new insight 
      regarding the specific contributions of the TRIF-Peli1 pathway to Meth-mediated 
      neuroinflammation.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Yang, Tingyu
AU  - Yang T
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Zang, Songsong
AU  - Zang S
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Wang, Yixin
AU  - Wang Y
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Zhu, Yuanhui
AU  - Zhu Y
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Jiang, Lei
AU  - Jiang L
AD  - Department of Emergency, The First Affiliated Hospital of Nanjing Medical 
      University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
FAU - Chen, Xufeng
AU  - Chen X
AD  - Department of Emergency, The First Affiliated Hospital of Nanjing Medical 
      University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.
FAU - Zhang, Xiaobao
AU  - Zhang X
AD  - Department of Anesthesiology, The First People's Hospital of Lianyungang, 
      Lianyungang, China.
FAU - Cheng, Jie
AU  - Cheng J
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Gao, Rong
AU  - Gao R
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Xiao, Hang
AU  - Xiao H
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China.
FAU - Wang, Jun
AU  - Wang J
AD  - Key Laboratory of Modern Toxicology (NJMU), Ministry of Education, Department of 
      Toxicology, School of Public Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China; China International Cooperation 
      Center for Environment and Human Health, Nanjing Medical University, 818 Tianyuan 
      East Road, Nanjing, Jiangsu, 211166, China. Electronic address: 
      wangjun@njmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200805
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Cytokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 6.3.2.- (Peli1 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics/*metabolism
MH  - Animals
MH  - Brain/*drug effects/immunology/metabolism
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Central Nervous System Stimulants/*toxicity
MH  - Cytokines/genetics
MH  - Gene Expression/drug effects
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Methamphetamine/*toxicity
MH  - Mice, Inbred C57BL
MH  - Microglia/*drug effects/immunology/metabolism
MH  - Nuclear Proteins/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - NF-kB and MAPK pathways
OT  - TRIF-Peli1 axis
OT  - methamphetamine
OT  - neuroinflammation
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- 2020/08/10 06:00
MHDA- 2020/11/03 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/03/30 00:00 [received]
PHST- 2020/06/29 00:00 [revised]
PHST- 2020/07/26 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2020/11/03 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0378-4274(20)30346-5 [pii]
AID - 10.1016/j.toxlet.2020.07.028 [doi]
PST - ppublish
SO  - Toxicol Lett. 2020 Oct 15;333:150-158. doi: 10.1016/j.toxlet.2020.07.028. Epub 
      2020 Aug 5.