PMID- 37490340
OWN - NLM
STAT- Publisher
LR  - 20231019
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 238
IP  - 10
DP  - 2023 Oct
TI  - Macrophage autophagy contributes to immune liver injury in trichloroethylene 
      sensitized mice: Critical role of TNF-alpha mediating mTOR pathway.
PG  - 2267-2281
LID - 10.1002/jcp.31083 [doi]
AB  - Trichloroethylene (TCE) induces occupational medicamentosa-like dermatitis due to 
      TCE (OMDT) with immune liver injury, and TNF-alpha plays an important role in 
      macrophage polarization and liver injury. However, TNF-alpha regulating macrophage 
      polarization in liver injury induced by TCE is still unknown. Thus, on the basis 
      of our previous research, we established the TCE-sensitized BALB/c mouse model 
      with R7050, a specific inhibitor of TNFR1. Then, we observed significant 
      decreases in autophagy related protein and gene levels in M1 macrophage in TCE 
      positive group, and R7050 can relieve M1 macrophage autophagy. We also found the 
      phosphorylated form of mammalian target of Rapamycin (mTOR) was activated and the 
      expression of p-mTOR protein increased induce by TCE. In vitro, we found TNFR1 
      and CD11c were increased in RAW264.7 cell line with TNF-alpha. And then we use 
      Zafirlukast (Zaf), an TNFR1 antagonist, CD11c and TNFR1 reduced significantly, we 
      also found p-mTOR expression increased after TNF-alpha treatment, but decreased in 
      TNF-alpha + Zaf group. Further, we used Rapamycin (RAP), a mTOR-specific inhibitor, 
      to establish a TCE-sensitized mice model and found the expression levels of p62 
      and p-mTOR proteins increased and LC3B decreased in the TCE positive group, while 
      RAP treatment reversed the trends of all of these proteins. Rapamycin prevented 
      the TNF-alpha-induced p-mTOR increase and dramatically downregulated IL-1beta expression 
      in the RAW264.7 cell line with TNF-alpha treatment. The results uncover a novel role 
      for TNF-alpha/TNFR1, which promotes M1 polarization of macrophage and suppresses 
      macrophage autophagy via the mTOR pathway.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Ding, Baiwang
AU  - Ding B
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Zhou, Sifan
AU  - Zhou S
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Wang, Zhoujian
AU  - Wang Z
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Liu, Wei
AU  - Liu W
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Gao, Lei
AU  - Gao L
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Ding, Yani
AU  - Ding Y
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Huang, Hua
AU  - Huang H
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
FAU - Zhu, Qixing
AU  - Zhu Q
AD  - Key Laboratory of Dermatology, Institute of Dermatology, Ministry of Education, 
      Hefei, Anhui, China.
AD  - Department of Dermatological, First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Zhang, Jiaxiang
AU  - Zhang J
AD  - Department of Occupational Health and Environmental Health, School of Public 
      Health, Anhui Medical University, Hefei, Anhui, China.
LA  - eng
GR  - 82273602/National Natural Science Foundation of China/
GR  - 82173494/National Natural Science Foundation of China/
GR  - 2008085QH385/Natural Science Foundation of Anhui Province/
GR  - XJ201941/Anhui Medical University/
PT  - Journal Article
DEP - 20230725
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
SB  - IM
OTO - NOTNLM
OT  - Trichloroethylene
OT  - autophagy
OT  - liver injury
OT  - mTOR
OT  - macrophage
EDAT- 2023/07/25 19:15
MHDA- 2023/07/25 19:15
CRDT- 2023/07/25 12:03
PHST- 2023/06/21 00:00 [revised]
PHST- 2023/03/17 00:00 [received]
PHST- 2023/07/07 00:00 [accepted]
PHST- 2023/07/25 19:15 [pubmed]
PHST- 2023/07/25 19:15 [medline]
PHST- 2023/07/25 12:03 [entrez]
AID - 10.1002/jcp.31083 [doi]
PST - ppublish
SO  - J Cell Physiol. 2023 Oct;238(10):2267-2281. doi: 10.1002/jcp.31083. Epub 2023 Jul 
      25.