PMID- 33182027
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210527
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 88
DP  - 2020 Nov
TI  - Canagliflozin alleviates LPS-induced acute lung injury by modulating alveolar 
      macrophage polarization.
PG  - 106969
LID - S1567-5769(20)31333-3 [pii]
LID - 10.1016/j.intimp.2020.106969 [doi]
AB  - BACKGROUND: Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, is 
      a novel therapeutic agent that exhibits multiple actions in type 2 diabetes. CANA 
      can regulate intracellular glucose metabolism and exert anti-inflammatory effects 
      in immune cells. Alveolar macrophage polarization balance is often associated 
      with lower inflammation in acute lung injury (ALI). However, little is known 
      about the anti-inflammatory effect of CANA on ALI. METHODS: This study aimed to 
      determine the effect of CANA on ALI as well as its potential ability to modulate 
      alveolar macrophage polarization in ALI mouse models and bone marrow-derived 
      macrophages (BMDMs). RESULTS: The histopathological changes indicated that CANA 
      alleviated lung injury in lipopolysaccharide-induced ALI mice models and exerted 
      anti-inflammatory effects in the presence of lower levels of tumor necrosis 
      factor-a, interleukin-6, and interleukin-1beta in bronchoalveolar lavage fluid 
      (BALF) and serum. Moreover, flow cytometry analysis of mouse BALF cells and BMDMs 
      demonstrated that CANA can modulate and reconstitute M1 and M2 macrophage 
      balance, inhibiting macrophages with the M1 phenotype while promoting macrophages 
      to shift to the M2 phenotype. Immunohistochemistry and reverse transcription 
      polymerase chain reaction were also performed. CONCLUSIONS: These findings 
      indicate that CANA alleviates lung injury and exerts anti-inflammatory effects by 
      modulating alveolar macrophage polarization balance, suggesting that CANA might 
      act as a novel anti-inflammatory drug for treating ALI.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Lin, Fengyu
AU  - Lin F
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China. Electronic address: linfengyu@csu.edu.cn.
FAU - Song, Chao
AU  - Song C
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China.
FAU - Zeng, Yanjun
AU  - Zeng Y
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China.
FAU - Li, Yi
AU  - Li Y
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China.
FAU - Li, Haitao
AU  - Li H
AD  - Cancer Hospital of Hunan Province, 410006, China.
FAU - Liu, Ben
AU  - Liu B
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China.
FAU - Dai, Minhui
AU  - Dai M
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China.
FAU - Pan, Pinhua
AU  - Pan P
AD  - Respiratory and Critical Care Medicine, Xiangya Hospital, Central South 
      University, 410008, China. Electronic address: pinhuapan668@csu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200911
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Acute Lung Injury/*drug therapy/immunology/pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Canagliflozin/pharmacology/*therapeutic use
MH  - Cytokines/blood/immunology
MH  - Lipopolysaccharides
MH  - Lung/drug effects/immunology/pathology
MH  - Macrophages, Alveolar/*drug effects/immunology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Phenotype
MH  - Sodium-Glucose Transporter 2 Inhibitors/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - Acute lung injury
OT  - Canagliflozin
OT  - Macrophage polarization
OT  - Sodium-glucose co-transporter 2 inhibitor
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- 2020/11/14 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/11/13 01:01
PHST- 2020/05/06 00:00 [received]
PHST- 2020/08/31 00:00 [revised]
PHST- 2020/08/31 00:00 [accepted]
PHST- 2020/11/14 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/11/13 01:01 [entrez]
AID - S1567-5769(20)31333-3 [pii]
AID - 10.1016/j.intimp.2020.106969 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Nov;88:106969. doi: 10.1016/j.intimp.2020.106969. Epub 
      2020 Sep 11.