PMID- 30557824
OWN - NLM
STAT- MEDLINE
DCOM- 20190509
LR  - 20190509
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 67
DP  - 2019 Feb
TI  - Rapamycin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting 
      IL-1beta and IL-18 production.
PG  - 211-219
LID - S1567-5769(18)31305-5 [pii]
LID - 10.1016/j.intimp.2018.12.017 [doi]
AB  - Interleukin (IL)-1beta and IL-18 play central and detrimental roles in the 
      development of acute lung injury (ALI), and mammalian target of rapamycin (mTOR) 
      is involved in regulating IL-1beta and IL-18 production. However, it is not clear 
      whether the mTOR specific inhibitor rapamycin can attenuate lipopolysaccharide 
      (LPS)-induced ALI by modulating IL-1beta and IL-18 production. In this study, we 
      found that rapamycin ameliorated LPS-induced ALI by inhibiting NOD-like receptor 
      family pyrin domain containing 3 (NLRP3) inflammasome-mediated IL-1beta and IL-18 
      secretion. Mechanistically, elevated autophagy and decreased nuclear factor 
      (NF)-kappaB activation were associated with downregulated IL-1beta and IL-18. Moreover, 
      rapamycin reduced leukocyte infiltration in the lung tissue and bronchoalveolar 
      lavage fluid (BALF), and contributed to the alleviation of LPS-induced ALI. 
      Consistently, rapamycin also significantly inhibited IL-1beta and IL-18 production 
      by RAW264.7 cells via increased autophagy and decreased NF-kappaB signaling in vitro. 
      Our results demonstrated that rapamycin protects mice against LPS-induced ALI 
      partly by inhibiting the production and secretion of IL-1beta and IL-18. mTOR and 
      rapamycin might represent an appropriate therapeutic target and strategy for 
      preventing ALI induced by LPS.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Jia, Xuehong
AU  - Jia X
AD  - Department of Respiratory Medicine, Beijing Tiantan Hospital, Capital Medical 
      University, Beijing 100050, China; Peking University China-Japan Friendship 
      School of Clinical Medicine, Beijing 100029, China.
FAU - Cao, Bin
AU  - Cao B
AD  - Department of Pulmonary and Critical Care Medicine, Center for Respiratory 
      Diseases, China-Japan Friendship Hospital, Beijing 100029, China; National 
      Clinical Research Center for Respiratory Diseases, Beijing 100029, China; 
      Department of Respiratory Medicine, Capital Medical University, Beijing 100069, 
      China.
FAU - An, Yunqing
AU  - An Y
AD  - Department of Immunology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, China.
FAU - Zhang, Xulong
AU  - Zhang X
AD  - Department of Immunology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing 100069, China. Electronic address: zhxlwl@ccmu.edu.cn.
FAU - Wang, Chen
AU  - Wang C
AD  - Peking University China-Japan Friendship School of Clinical Medicine, Beijing 
      100029, China; Department of Pulmonary and Critical Care Medicine, Center for 
      Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China; 
      National Clinical Research Center for Respiratory Diseases, Beijing 100029, 
      China; Department of Respiratory Medicine, Capital Medical University, Beijing 
      100069, China; Chinese Academy of Medical Sciences, Peking Union Medical College, 
      Beijing 100730, China. Electronic address: cyh-birm@263.net.
LA  - eng
PT  - Journal Article
DEP - 20181215
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Acute Lung Injury/*chemically induced/*prevention & control
MH  - Animals
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-18/genetics/*metabolism
MH  - Interleukin-1beta/genetics/*metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Sirolimus/*pharmacology
OTO - NOTNLM
OT  - Acute lung injury
OT  - Autophagy
OT  - IL-18
OT  - IL-1beta
OT  - NF-kappaB
OT  - mTOR
EDAT- 2018/12/18 06:00
MHDA- 2019/05/10 06:00
CRDT- 2018/12/18 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/11/30 00:00 [revised]
PHST- 2018/12/07 00:00 [accepted]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2019/05/10 06:00 [medline]
PHST- 2018/12/18 06:00 [entrez]
AID - S1567-5769(18)31305-5 [pii]
AID - 10.1016/j.intimp.2018.12.017 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2019 Feb;67:211-219. doi: 10.1016/j.intimp.2018.12.017. Epub 
      2018 Dec 15.