PMID- 30579975
OWN - NLM
STAT- MEDLINE
DCOM- 20190903
LR  - 20190903
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 141
DP  - 2019 Mar
TI  - Pharmacological preconditioning with the cellular stress inducer thapsigargin 
      protects against experimental sepsis.
PG  - 114-122
LID - S1043-6618(18)31472-5 [pii]
LID - 10.1016/j.phrs.2018.12.017 [doi]
AB  - Previous studies have shown that pretreatment with thapsigargin (TG), a cellular 
      stress inducer, produced potent protective actions against various pathologic 
      injuries. So far there is no information on the effects of TG on the development 
      of bacterial sepsis. Using lipopolysaccharides- and cecal 
      ligation/puncture-induced sepsis models in mice, we demonstrated that 
      preconditioning with a single bolus administration of TG conferred significant 
      improvements in survival. The beneficial effects of TG were not mediated by ER 
      stress induction or changes in Toll-like receptor 4 signaling. In vivo and in 
      cultured macrophages, we identified that TG reduced the protein production of 
      pro-inflammatory cytokines, but exhibited no significant effects on steady state 
      levels of their transcriptions. Direct measurement on the fraction of 
      polysome-bound mRNAs revealed that TG reduced the translational efficiency of 
      pro-inflammatory cytokines in macrophages. Moreover, we provided evidence 
      suggesting that repression of the mTOR (the mammalian target of rapamycin) 
      signaling pathway, but not activation of the PERK (protein kinase R-like 
      endoplasmic reticulum kinase)-eIF2alpha (eukaryotic initiation factor 2alpha) pathway, 
      might be involved in mediating the TG effects on cytokine production. In summary, 
      our results support that pharmacological preconditioning with TG may represent a 
      novel strategy to prevent sepsis-induced mortality and organ injuries.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Wei, Yaping
AU  - Wei Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Meng, Mei
AU  - Meng M
AD  - Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated, 
      Shandong University, Jinan, Shandong Province, China.
FAU - Tian, Zhenyu
AU  - Tian Z
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, Jinan, China.
FAU - Xie, Fubo
AU  - Xie F
AD  - Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 
      Province, China.
FAU - Yin, Qihui
AU  - Yin Q
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Dai, Chaochao
AU  - Dai C
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Zhang, Qunye
AU  - Zhang Q
AD  - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese 
      Ministry of Education, Chinese National Health Commission and Chinese Academy of 
      Medical Sciences, The State and Shandong Province Joint Key Laboratory of 
      Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of 
      Shandong University, Jinan, China.
FAU - Liu, Yu
AU  - Liu Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China.
FAU - Yan, Feng
AU  - Yan F
AD  - Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 
      Province, China.
FAU - Jiang, Fan
AU  - Jiang F
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China; The Key Laboratory of Cardiovascular 
      Remodeling and Function Research, Chinese Ministry of Education, Chinese National 
      Health Commission and Chinese Academy of Medical Sciences, The State and Shandong 
      Province Joint Key Laboratory of Translational Cardiovascular Medicine, 
      Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. 
      Electronic address: fjiang@sdu.edu.cn.
FAU - Guo, Xiaosun
AU  - Guo X
AD  - Department of Physiology and Pathophysiology, School of Basic Medicine, Shandong 
      University, Jinan, Shandong Province, China. Electronic address: 
      guoxiaosun@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181221
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Protective Agents)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Cytokines/physiology
MH  - Disease Models, Animal
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/drug effects
MH  - Pre-Exposure Prophylaxis
MH  - Protective Agents/*therapeutic use
MH  - RAW 264.7 Cells
MH  - Sepsis/*drug therapy
MH  - Thapsigargin/*therapeutic use
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - 4-Phenylbutyric acid (CID:4775)
OT  - Pharmacological preconditioning
OT  - Protein translational efficiency
OT  - Sepsis
OT  - Systemic inflammation response
OT  - Thapsigargin
OT  - Thapsigargin (CID: 446378)
OT  - mTOR
EDAT- 2018/12/24 06:00
MHDA- 2019/09/04 06:00
CRDT- 2018/12/24 06:00
PHST- 2018/09/27 00:00 [received]
PHST- 2018/12/12 00:00 [revised]
PHST- 2018/12/19 00:00 [accepted]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2019/09/04 06:00 [medline]
PHST- 2018/12/24 06:00 [entrez]
AID - S1043-6618(18)31472-5 [pii]
AID - 10.1016/j.phrs.2018.12.017 [doi]
PST - ppublish
SO  - Pharmacol Res. 2019 Mar;141:114-122. doi: 10.1016/j.phrs.2018.12.017. Epub 2018 
      Dec 21.