PMID- 31813830
OWN - NLM
STAT- MEDLINE
DCOM- 20201021
LR  - 20211204
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 78
DP  - 2020 Jan
TI  - Mechanistic target of rapamycin-mediated autophagy is involved in the alleviation 
      of lipopolysaccharide-induced acute lung injury in rats.
PG  - 105790
LID - S1567-5769(19)30976-2 [pii]
LID - 10.1016/j.intimp.2019.105790 [doi]
AB  - Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and 
      mortality rates. Autophagy is an adaptive process that plays a complex role in 
      ALI. The aim of this study was to investigate the effects of autophagy on 
      lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and 
      to further explore the possible mechanisms involved. Rats were pretreated with 
      the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy activator 
      rapamycin before they were challenged with the intratracheal instillation of LPS 
      (5 mg/kg). The level of autophagy in the lung tissue was detected. Lung injury 
      and vascular permeability were assessed. The role of the mechanistic target of 
      rapamycin (mTOR)-mediated Unc-51-like kinase 1 (ULK1) and the class III PI3 
      kinase VPS34 in autophagy regulation was examined. LPS challenge induced 
      autophagy and rapamycin pretreatment enhanced autophagy activity in LPS-induced 
      ALI rats. LPS caused severe lung injury and high pulmonary vascular permeability, 
      which could be alleviated by enhancing autophagy. In addition, the inhibition of 
      mTOR upregulated the expression of ULK1 and VPS34 and thus increased LPS-induced 
      autophagy. Autophagy plays a protective role in LPS-induced ALI, and enhancing 
      autophagy via the inhibition of mTOR alleviates lung injury and pulmonary barrier 
      function. Moreover, mTOR negatively mediates ULK1 and VPS34 to regulate 
      LPS-induced autophagy in rats.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Qin, Li
AU  - Qin L
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China.
FAU - Li, Min
AU  - Li M
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China.
FAU - Tan, Hong-Ling
AU  - Tan HL
AD  - Institute of Radiation Medicine Sciences, Academy of Military Medical Sciences, 
      No. 27 Taiping Road, Haidian district, Beijing 100850, People's Republic of 
      China.
FAU - Yang, Hong-Xing
AU  - Yang HX
AD  - Institute of First Clinical Medical Colleges, Beijing University of Chinese 
      Medicine, Beisanhuan east road, Chaoyang district, Beijing 100029, People's 
      Republic of China.
FAU - Li, Shao-Dan
AU  - Li SD
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China.
FAU - Luan, Zhen-Xian
AU  - Luan ZX
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China.
FAU - Chen, Ying-Fan
AU  - Chen YF
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China.
FAU - Yang, Ming-Hui
AU  - Yang MH
AD  - Institute of Traditional Chinese Medicine, Chinese PLA General Hospital, No. 28 
      Fuxin Road, Haidian district, Beijing 100853, People's Republic of China. 
      Electronic address: ymh9651@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20191206
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (IL1B protein, rat)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ULK1 protein, rat)
SB  - IM
MH  - Acute Lung Injury/chemically induced/*immunology/pathology
MH  - Animals
MH  - *Autophagy
MH  - Autophagy-Related Protein-1 Homolog/immunology
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Class III Phosphatidylinositol 3-Kinases/immunology
MH  - Interleukin-1beta/immunology
MH  - Lipopolysaccharides
MH  - Lung/immunology/pathology
MH  - Male
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/*immunology
MH  - Tumor Necrosis Factor-alpha/immunology
OTO - NOTNLM
OT  - 3-Methyladenine
OT  - Acute lung injury
OT  - Autophagy
OT  - Lipopolysaccharide
OT  - Mechanistic target of rapamycin
OT  - Rapamycin
EDAT- 2019/12/10 06:00
MHDA- 2020/10/22 06:00
CRDT- 2019/12/10 06:00
PHST- 2019/05/06 00:00 [received]
PHST- 2019/07/22 00:00 [revised]
PHST- 2019/07/25 00:00 [accepted]
PHST- 2019/12/10 06:00 [pubmed]
PHST- 2020/10/22 06:00 [medline]
PHST- 2019/12/10 06:00 [entrez]
AID - S1567-5769(19)30976-2 [pii]
AID - 10.1016/j.intimp.2019.105790 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Jan;78:105790. doi: 10.1016/j.intimp.2019.105790. Epub 
      2019 Dec 6.