PMID- 34861244
OWN - NLM
STAT- MEDLINE
DCOM- 20220119
LR  - 20220119
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 195
DP  - 2022 Jan
TI  - Maresin 1 protects against lipopolysaccharide/d-galactosamine-induced acute liver 
      injury by inhibiting macrophage pyroptosis and inflammatory response.
PG  - 114863
LID - S0006-2952(21)00489-5 [pii]
LID - 10.1016/j.bcp.2021.114863 [doi]
AB  - BACKGROUND: Acute liver injury (ALI) caused by sepsis is a fearful disease with 
      high mortality and poor prognosis. This study aimed to explore the roles and 
      mechanism of Maresin 1 (MaR1) in lipopolysaccharide/d-galactosamine 
      (LPS/D-GalN)-induced ALI. METHODS: We established an ALI mouse model induced by 
      LPS/D-GalN. Each group was treated with or without LPS/D-GalN or MaR1. For the 
      vitro experiments, RAW264.7, NCTC1469 cells, and bone marrow-derived macrophages 
      (BMDMs) were stimulated with LPS. The effects of MaR1 on the reactive oxygen 
      species (ROS), pyroptosis and inflammatory response in macrophages were 
      investigated. RESULTS: MaR1 significantly inhibited an excessive inflammatory 
      response and proinflammatory markers during LPS/D-GalN-induced ALI. MaR1 markedly 
      decreased the levels of ROS, tumor necrosis factor-alpha, and interleukin-1beta (IL-1beta) 
      in macrophages, and limited hepatocyte apoptosis in vitro. Upon exploring the 
      mechanisms underlying the protective role of MaR1, we found MaR1 markedly 
      upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme 
      oxygenase-1 (HO-1), and considerably reduced the phosphorylation of p38, ERK, and 
      nuclear factor-kappa B (NF-kappaB)-p65. Knocking down Nrf2 decreased the effect of 
      MaR1. Furthermore, we observed that MaR1 reduced inflammatory injury by 
      inhibiting M1 macrophages and promoting M2 macrophage polarization. Finally, we 
      observed that MaR1 could inhibit the production of gasdermin D N-terminus 
      (GSDMD-N) in vivo. In vitro, MaR1 could significantly suppressed the expression 
      of NLR family pyrin domain containing 3 (NLRP3) inflammasome, GSDMD-N, and IL-1beta 
      caused by LPS and nigericin stimulation in BMDMs. CONCLUSION: MaR1 could 
      ameliorate inflammation during LPS/D-GalN induced ALI by suppressing 
      mitogen-activated protein kinase /NF-kappaB signaling and NLRP3 inflammasome-induced 
      pyroptosis, activating macrophage M1/M2 polarization and Nrf2/HO-1 signaling. 
      This provides new evidence for the potential of developing MaR1 for ALI 
      treatment.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Yang, Wenchang
AU  - Yang W
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Tao, Kaixiong
AU  - Tao K
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Chen, Xin
AU  - Chen X
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Sun, Xiong
AU  - Sun X
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Li, Ruidong
AU  - Li R
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China. Electronic 
      address: liruidong@hust.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211130
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid)
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Protective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemical and Drug Induced Liver Injury/etiology/*prevention & control
MH  - Cytokines/metabolism
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Galactosamine
MH  - Heme Oxygenase-1/metabolism
MH  - Inflammasomes/*drug effects/metabolism
MH  - Lipopolysaccharides
MH  - Liver/drug effects/metabolism/pathology
MH  - Macrophages/*drug effects
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Protective Agents/pharmacology
MH  - Pyroptosis/*drug effects
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Acute liver injury
OT  - LPS/D-GalN
OT  - Maresin 1
OT  - NF-kappaB
OT  - Pyroptosis
EDAT- 2021/12/04 06:00
MHDA- 2022/01/20 06:00
CRDT- 2021/12/03 20:12
PHST- 2021/09/11 00:00 [received]
PHST- 2021/11/22 00:00 [revised]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/12/04 06:00 [pubmed]
PHST- 2022/01/20 06:00 [medline]
PHST- 2021/12/03 20:12 [entrez]
AID - S0006-2952(21)00489-5 [pii]
AID - 10.1016/j.bcp.2021.114863 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2022 Jan;195:114863. doi: 10.1016/j.bcp.2021.114863. Epub 2021 
      Nov 30.