PMID- 37051243
OWN - NLM
STAT- MEDLINE
DCOM- 20230414
LR  - 20230417
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Alpha-linolenic acid pretreatment alleviates NETs-induced alveolar macrophage 
      pyroptosis by inhibiting pyrin inflammasome activation in a mouse model of 
      sepsis-induced ALI/ARDS.
PG  - 1146612
LID - 10.3389/fimmu.2023.1146612 [doi]
LID - 1146612
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) can cause acute lung injury 
      (ALI)/acute respiratory distress syndrome (ARDS) by inducing macrophage 
      pyroptosis. The purpose of this study was to find out whether pretreatment of 
      alpha-linolenic acid (ALA) could inhibit NETs-induced macrophage pyroptosis in 
      sepsis-induced ALI/ARDS, as well as to identify which inflammasome is involved in 
      this process. METHODS: LPS was instilled into the trachea to establish 
      sepsis-induced ALI/ARDS in a mouse model. ​Lung injury was assessed by 
      microscopic examination of lung tissue after hematoxylin and eosin staining, 
      pathology score, and bronchoalveolar lavage fluid (BALF) total protein 
      concentration. The level of NETs in lung tissue was detected by MPO-DNA ELISA. 
      Purified NETs, extracted from peritoneal neutrophils, induced macrophage 
      pyroptosis in vitro. Expression of pyroptosis-related proteins (Cl-caspase-1, 
      Cl-GSDMD, ASC) and IL-1beta in the lung tissue and bone marrow-derived macrophages 
      (BMDMs) were determined by western blotting or ELISA. Specks of Pyrin/ASC were 
      examined by confocal immunofluorescence microscopy. Mefv (Pyrin)(-/-) mice were 
      used to study the role of Pyrin in the process of sepsis-induced ALI/ARDS. 
      RESULTS: ALA alleviated LPS-induced lung injury. ALA reduced the level of NETs, 
      pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC), and IL-1beta in the lung 
      tissue of sepsis mice. In vitro, NETs increased the expression of 
      pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) and IL-1beta significantly 
      in BMDMs. Pyrin protein was found to be higher and form the inflammasome with ASC 
      in NETs challenged-BMDMs. Knockout of Mefv (Pyrin) gene fully restored the 
      increased expression of pyroptosis-related proteins (Cl-caspase-1, Cl-GSDMD, ASC) 
      and IL-1beta in vitro and in vivo. Lung injury was alleviated significantly in Mefv 
      (Pyrin)-/- mice as well.​ ALA suppresses all the NETs-induced changes as 
      mentioned above. CONCLUSION: Our study is the first to demonstrate Pyrin 
      inflammasome driving NETs-induced macrophage pyroptosis, and ALA may reduce 
      ALI/ARDS by inhibiting the activation of the Pyrin inflammasome-driven macrophage 
      pyroptosis.
CI  - Copyright (c) 2023 Liu, Zhou, Tu, Yao, Li and Yang.
FAU - Liu, Chenchen
AU  - Liu C
AD  - School of Anesthesiology, Weifang Medical University, Weifang, China.
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Zhou, Yu
AU  - Zhou Y
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Tu, Qing
AU  - Tu Q
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Yao, Liangfang
AU  - Yao L
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Li, Jinbao
AU  - Li J
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
FAU - Yang, Zhongwei
AU  - Yang Z
AD  - Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiaotong 
      University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230327
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Inflammasomes)
RN  - 0 (Pyrin)
RN  - 0RBV727H71 (alpha-Linolenic Acid)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Lipopolysaccharides)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Inflammasomes/metabolism
MH  - Macrophages, Alveolar/metabolism
MH  - Pyrin
MH  - alpha-Linolenic Acid
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - *Extracellular Traps/metabolism
MH  - Pyroptosis
MH  - Lipopolysaccharides/pharmacology
MH  - *Acute Lung Injury/metabolism
MH  - Mice, Knockout
MH  - *Respiratory Distress Syndrome/pathology
MH  - *Sepsis/complications/pathology
MH  - Caspases
PMC - PMC10083395
OTO - NOTNLM
OT  - ARDS
OT  - NETs
OT  - alpha-linolenic acid (ALA)
OT  - pyrin
OT  - pyroptosis
OT  - sepsis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:41
PMCR- 2023/01/01
CRDT- 2023/04/13 01:59
PHST- 2023/01/17 00:00 [received]
PHST- 2023/03/14 00:00 [accepted]
PHST- 2023/04/14 06:41 [medline]
PHST- 2023/04/13 01:59 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1146612 [doi]
PST - epublish
SO  - Front Immunol. 2023 Mar 27;14:1146612. doi: 10.3389/fimmu.2023.1146612. 
      eCollection 2023.