PMID- 32705226
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 22
IP  - 3
DP  - 2020 Sep
TI  - Suppression of sirtuin 1 alleviates airway inflammation through mTOR‑mediated 
      autophagy.
PG  - 2219-2226
LID - 10.3892/mmr.2020.11338 [doi]
AB  - Sirtuin 1 (SIRT1) is involved in the pathogenesis of allergic asthma. This study 
      aimed to investigate whether EX‑527, a specific SIRT1 inhibitor, exerted 
      suppressive effects on allergic airway inflammation in mice submitted to 
      ovalbumin (OVA) inhalation. In addition, this study assessed whether such a 
      protective role was mediated by autophagy suppression though mammalian target of 
      rapamycin (mTOR) activation. Female C57BL/6 mice were sensitized to OVA and 
      EX‑527 (10 mg/kg) was administered prior to OVA challenge. The study found that 
      EX‑527 reversed OVA‑induced airway inflammation, and reduced OVA‑induced 
      increases in inflammatory cytokine expression, and total cell and eosinophil 
      counts in bronchoalveolar lavage fluid. In addition, EX‑527 enhanced mTOR 
      activation, thereby suppressing autophagy in allergic mice. To assess whether 
      EX‑527 inhibited airway inflammation in asthma through the mTOR‑mediated 
      autophagy pathway, rapamycin was administered to mice treated with EX‑527 after 
      OVA sensitization. All effects induced by EX‑527, including increased 
      phosphorylated‑mTOR and decreased autophagy, were abrogated by rapamycin 
      treatment. Taken together, the present findings indicated that EX‑527 may inhibit 
      allergic airway inflammation by suppressing autophagy, an effect mediated by mTOR 
      activation in allergic mice.
FAU - Wu, Yuanyuan
AU  - Wu Y
AD  - Department of Respiratory and Critical Care Medicine, The Second Affiliated 
      Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, 
      P.R. China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Respiratory and Critical Care Medicine, The Second Affiliated 
      Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, 
      P.R. China.
FAU - Hu, Yifan
AU  - Hu Y
AD  - Department of Respiratory and Critical Care Medicine, The Second Affiliated 
      Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, 
      P.R. China.
FAU - Liu, Yun
AU  - Liu Y
AD  - Department of Respiratory and Critical Care Medicine, The Second Affiliated 
      Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, 
      P.R. China.
FAU - Sun, Xiuzhen
AU  - Sun X
AD  - Department of Respiratory and Critical Care Medicine, The Second Affiliated 
      Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200713
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide)
RN  - 0 (Carbazoles)
RN  - 0 (Cytokines)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Asthma/chemically induced
MH  - Autophagy
MH  - Carbazoles/*administration & dosage/pharmacology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovalbumin/*adverse effects
MH  - Phosphorylation
MH  - Sirolimus/*administration & dosage/pharmacology
MH  - Sirtuin 1/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC7411491
OTO - NOTNLM
OT  - asthma
OT  - sirtuin 1
OT  - airway inflammation
OT  - autophagy
OT  - mammalian target of rapamycin
EDAT- 2020/07/25 06:00
MHDA- 2021/04/22 06:00
PMCR- 2020/07/13
CRDT- 2020/07/25 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2020/04/15 00:00 [accepted]
PHST- 2020/07/25 06:00 [entrez]
PHST- 2020/07/25 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
PHST- 2020/07/13 00:00 [pmc-release]
AID - mmr-22-03-2219 [pii]
AID - 10.3892/mmr.2020.11338 [doi]
PST - ppublish
SO  - Mol Med Rep. 2020 Sep;22(3):2219-2226. doi: 10.3892/mmr.2020.11338. Epub 2020 Jul 
      13.