PMID- 34920961
OWN - NLM
STAT- MEDLINE
DCOM- 20220201
LR  - 20220531
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 24
IP  - 2
DP  - 2022 Feb
TI  - Sirtuin 6 regulates macrophage polarization to alleviate sepsis-induced acute 
      respiratory distress syndrome via dual mechanisms dependent on and independent of 
      autophagy.
PG  - 149-160
LID - S1465-3249(21)00779-9 [pii]
LID - 10.1016/j.jcyt.2021.09.001 [doi]
AB  - BACKGROUND AIMS: Sepsis-induced acute respiratory distress syndrome (ARDS) can be 
      mediated by an imbalance in macrophage polarization; however, the underlying 
      mechanisms remain poorly understood. This study aimed to investigate the 
      modulatory role of sirtuin 6 (SIRT6) in macrophage polarization during 
      sepsis-induced ARDS. METHODS: A mouse ARDS model was established using cecal 
      ligation and puncture. Isolated alveolar macrophages (AMs) and lipopolysaccharide 
      (LPS)-stimulated bone marrow-derived macrophages (BMDMs) were adopted as in vitro 
      models. Macrophage polarization was evaluated by measuring M1 and M2 macrophage 
      percentages via flow cytometry and expression of specific markers. The expression 
      of microtubule-associated light chain protein 3I/II and beclin-1 was detected for 
      assessing macrophage autophagy. Binding between specificity protein 1 (SP1) and 
      the target gene promoter was evaluated using a chromatin immunoprecipitation 
      assay. RNA expression was analyzed by quantitative reverse transcription 
      polymerase chain reaction and western blotting. RESULTS: Treatment with the SIRT6 
      activator UBCS039 significantly alleviated lung injury in the mouse ARDS model 
      and enhanced autophagy and M2 polarization in isolated AMs. M2 polarization and 
      autophagy in LPS-challenged BMDMs were also effectively promoted by UBCS039 
      treatment or SIRT6 overexpression. An adenosine monophosphate-activated protein 
      kinase inhibitor (Compound C) or autophagy inhibitor (3-methyladenine) partially 
      abrogated M2 polarization mediated by SIRT6 overexpression upon LPS exposure. 
      SIRT6 induced autophagy and M2 polarization of BMDMs partially via its 
      deacetylase activity. SIRT6 inhibited mammalian target of rapamycin transcription 
      by modulating SP1 to promote BMDM M2 polarization, which was independent of 
      autophagy. CONCLUSIONS: SIRT6 promotes M2 polarization of macrophages to 
      alleviate sepsis-induced ARDS in an autophagy-dependent and -independent manner.
CI  - Copyright (c) 2021 International Society for Cell & Gene Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Wang, Qian-Lu
AU  - Wang QL
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Yang, Lei
AU  - Yang L
AD  - Department of Preparations, The First Hospital of Hunan University of Chinese 
      Medicine, Changsha, China.
FAU - Liu, Zuo-Liang
AU  - Liu ZL
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Peng, Yue
AU  - Peng Y
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Gao, Min
AU  - Gao M
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Deng, Long-Tian
AU  - Deng LT
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Liu, Xi
AU  - Liu X
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China.
FAU - Xing, Wei
AU  - Xing W
AD  - Department of Intensive Care Medicine, The Third Xiangya Hospital of Central 
      South University, Changsha, China. Electronic address: xy3yyxw@csu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211214
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - EC 2.4.2.31 (Sirt6 protein, mouse)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Macrophages
MH  - Mice
MH  - *Respiratory Distress Syndrome/etiology/therapy
MH  - *Sepsis/complications
MH  - *Sirtuins
OTO - NOTNLM
OT  - SIRT6
OT  - acute lung injury
OT  - autophagy
OT  - macrophage polarization
OT  - sepsis-induced ARDS
COIS- Declaration of Competing Interest The authors have no commercial, proprietary or 
      financial interest in the products or companies described in this article.
EDAT- 2021/12/19 06:00
MHDA- 2022/02/02 06:00
CRDT- 2021/12/18 05:31
PHST- 2021/02/21 00:00 [received]
PHST- 2021/08/11 00:00 [revised]
PHST- 2021/09/04 00:00 [accepted]
PHST- 2021/12/19 06:00 [pubmed]
PHST- 2022/02/02 06:00 [medline]
PHST- 2021/12/18 05:31 [entrez]
AID - S1465-3249(21)00779-9 [pii]
AID - 10.1016/j.jcyt.2021.09.001 [doi]
PST - ppublish
SO  - Cytotherapy. 2022 Feb;24(2):149-160. doi: 10.1016/j.jcyt.2021.09.001. Epub 2021 
      Dec 14.