PMID- 38232538
OWN - NLM
STAT- MEDLINE
DCOM- 20240213
LR  - 20240213
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 128
DP  - 2024 Feb 15
TI  - Apolipoprotein C3 (ApoC3) facilitates NLRP3 mediated pyroptosis of macrophages 
      through mitochondrial damage by accelerating of the interaction between SCIMP and 
      SYK pathway in acute lung injury.
PG  - 111537
LID - S1567-5769(24)00055-9 [pii]
LID - 10.1016/j.intimp.2024.111537 [doi]
AB  - Respiratory failure caused by severe acute lung injury (ALI) is the main cause of 
      mortality in patients with COVID-19.This study aimed to investigate the effects 
      and underlying biological mechanism of Apolipoprotein C3 (ApoC3) in ALI. To 
      establish an in vivo model, C57BL/6 mice were exposed by lipopolysaccharide 
      (LPS). For the in vitro model, murine bone marrow-derived macrophages (BMDMs) or 
      RAW264.7 cells were stimulated with LPS + adenosine triphosphate (ATP). Serum 
      levels of ApoC3 were found to be upregulated in patients with COVID-19 or 
      pneumonia-induced ALI. Inhibition of ApoC3 reduced lung injury in an ALI model, 
      while overexpression of ApoC3 promoted lung injury. ApoC3 induced mitochondrial 
      damage-mediated pyroptosis in ALI through the activation of the NOD-like 
      receptorprotein 3 (NLRP3) inflammasome. ApoC3 recombinant protein significantly 
      increased SCIMP expression in the lung tissue of mice models with ALI. ApoC3 also 
      facilitated the interaction between the SLP adapter and CSK-interacting membrane 
      protein (SCIMP) protein and Spleen tyrosine kinase (SYK) protein in the ALI 
      model. Moreover, ApoC3 accelerated calcium-dependent reactive oxygen species 
      (ROS) production in the ALI model. The effects of ApoC3 on pyroptosis were 
      mitigated by the use of a pyroptosis inhibitor or an ROS inhibitor in the ALI 
      model. Furthermore, ApoC3 activated the expression of SYK, which in turn induced 
      NLRP3 inflammasome-regulated pyroptosis in the ALI model. METTL3 was found to 
      mediate the m6A mRNA expression of ApoC3. Overall, our study highlights the 
      crucial role of ApoC3 in promoting macrophage pyroptosis in ALI through 
      calcium-dependent ROS production and NLRP3 inflammasome activation via the 
      SCIMP-SYK pathway, providing a potential therapeutic strategy for ALI and other 
      inflammatory diseases.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Pu, Zhichen
AU  - Pu Z
AD  - Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 
      Anhui 241001, China; Key Laboratory of Non-coding RNA Transformation Research of 
      Anhui Higher Education Institution, Wannan Medical College, Wuhu 241001, China; 
      State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and 
      Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 
      210009, China.
FAU - Wang, Wenhui
AU  - Wang W
AD  - Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 
      Anhui 241001, China.
FAU - Xie, Haitang
AU  - Xie H
AD  - Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, 
      Anhui 241001, China. Electronic address: xhaitang@yeah.net.
FAU - Wang, Wusan
AU  - Wang W
AD  - Department of Pharmacology, Wannan Medical College, Wuhu, Anhui 241001, China. 
      Electronic address: wangyue206@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20240116
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.62 (METTL3 protein, human)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - 0 (APOC3 protein, human)
RN  - 0 (Apolipoproteins C)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Acute Lung Injury/drug therapy
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Calcium/metabolism
MH  - *COVID-19
MH  - Inflammasomes/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages
MH  - Membrane Proteins/metabolism
MH  - *Methyltransferases
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Pyroptosis
MH  - Reactive Oxygen Species/metabolism
MH  - Syk Kinase/metabolism
MH  - Apolipoproteins C/metabolism
OTO - NOTNLM
OT  - Acute lung injury
OT  - ApoC3
OT  - COVID-19
OT  - Mitochondrial damage
OT  - Pyroptosis
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- 2024/01/18 00:42
MHDA- 2024/02/08 06:42
CRDT- 2024/01/17 18:06
PHST- 2023/09/03 00:00 [received]
PHST- 2023/12/25 00:00 [revised]
PHST- 2024/01/10 00:00 [accepted]
PHST- 2024/02/08 06:42 [medline]
PHST- 2024/01/18 00:42 [pubmed]
PHST- 2024/01/17 18:06 [entrez]
AID - S1567-5769(24)00055-9 [pii]
AID - 10.1016/j.intimp.2024.111537 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2024 Feb 15;128:111537. doi: 10.1016/j.intimp.2024.111537. 
      Epub 2024 Jan 16.