PMID- 32102753
OWN - NLM
STAT- MEDLINE
DCOM- 20201111
LR  - 20201111
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 525
IP  - 2
DP  - 2020 Apr 30
TI  - Increased macrophage activation mediated by caspase recruitment domain 6 
      knockdown through negatively targeting AMPK.
PG  - 412-417
LID - S0006-291X(20)30354-5 [pii]
LID - 10.1016/j.bbrc.2020.02.080 [doi]
AB  - Caspase recruitment domain 6 (CARD6) was initially implicated in the immune 
      system and oncogenesis, which has also been emerged to play an important role in 
      cardio-metabolic diseases. Nevertheless, the potential role of CARD6 on 
      macrophage activation remains unknown. In the present study, we observed a 
      decreased CARD6 expression in bone marrow derived macrophages (BMDMs) and mouse 
      peritoneal macrophages (MPMs) isolated from ApoE deficiency mice and 
      administrated with OX-LDL, which were tested by RT-PCR and western bolt analysis. 
      Moreover, the immunofluorescence co-staining revealed that a weaker 
      immunoreactivity of CARD6 was found and primary located in cytoplasm of 
      macrophages induced by OX-LDL. Phenotypically, loss-of-function of CARD6 
      dramatically increased pro-inflammatory M1 macrophage but decreased resolving M2 
      macrophage markers expression. Additionally, CARD6 knockdown significantly 
      promoted cholesterol uptake but attenuated cholesterol efflux, which lead to 
      increased foam cell formation. Mechanistically, a downregulated AMP-activated 
      protein kinase (AMPK) expression was required for the promoted effect of CARD6 
      knockdown on macrophage activation. Taken together, these results suggest that 
      CARD6 protects against macrophage activation partially through activation of 
      AMPK-dependent mechanism.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Chen, Fangyuan
AU  - Chen F
AD  - Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an 
      Jiaotong University, 710061, China. Electronic address: 
      chen_fang_yuan_xa@126.com.
FAU - Li, Juanli
AU  - Li J
AD  - Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an 
      Jiaotong University, 710061, China.
FAU - Tian, Gang
AU  - Tian G
AD  - Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an 
      Jiaotong University, 710061, China.
FAU - Yuan, Zuyi
AU  - Yuan Z
AD  - Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an 
      Jiaotong University, 710061, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200223
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Card6 protein, mouse)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*immunology
MH  - Animals
MH  - CARD Signaling Adaptor Proteins/genetics/*immunology
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Gene Knockdown Techniques
MH  - Inflammation/genetics/*immunology
MH  - Lipoproteins, LDL/immunology
MH  - *Macrophage Activation
MH  - Macrophages/immunology/metabolism
MH  - Mice
OTO - NOTNLM
OT  - AMPK
OT  - Atherosclerosis
OT  - CARD6
OT  - Macrophage
COIS- Declaration of competing interest None.
EDAT- 2020/02/28 06:00
MHDA- 2020/11/12 06:00
CRDT- 2020/02/28 06:00
PHST- 2019/12/27 00:00 [received]
PHST- 2020/02/06 00:00 [revised]
PHST- 2020/02/12 00:00 [accepted]
PHST- 2020/02/28 06:00 [pubmed]
PHST- 2020/11/12 06:00 [medline]
PHST- 2020/02/28 06:00 [entrez]
AID - S0006-291X(20)30354-5 [pii]
AID - 10.1016/j.bbrc.2020.02.080 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Apr 30;525(2):412-417. doi: 
      10.1016/j.bbrc.2020.02.080. Epub 2020 Feb 23.