PMID- 20828737
OWN - NLM
STAT- MEDLINE
DCOM- 20120106
LR  - 20211203
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 171
IP  - 2
DP  - 2011 Dec
TI  - Role of the mTOR pathway in LPS-activated monocytes: influence of hypertonic 
      saline.
PG  - 769-76
LID - 10.1016/j.jss.2010.05.035 [doi]
AB  - BACKGROUND: As heightened protein synthesis is the hallmark of many inflammatory 
      syndromes, we hypothesize that the mammalian target of rapamycin (mTOR) pathway, 
      which control the cap-dependent translation initiation phase, was activated by 
      lipopolysaccharide (LPS). In addition, we studied the effect of hypertonic saline 
      solution (HTS) on the mTOR cascade in peripheral blood mononuclear cells (PBMCs). 
      MATERIALS AND METHODS: PBMCs were isolated from healthy volunteers and treated 
      with LPS. Cells were pretreated with phosphatidylinositol 3-kinase (PI3K) and 
      mTOR inhibitors, or with HTS. Supernatants were harvested 20 h following LPS 
      treatment, and interleukin-10 (IL-10), interleukin-6 (IL-6) and tumor necrosis 
      alpha (TNFalpha) were analyzed by ELISA. Immunoblot experiments were performed for 
      components of the PI3K/Akt/mTOR pathway at various time points. RNA was extracted 
      after 90 min for real-time RT-PCR quantification. RESULTS: The mTOR pathway is 
      activated in PBMCs within 1 h of LPS stimulation. Pretreatment with rapamycin, a 
      specific inhibitor of mTOR, resulted in a significant decrease of IL-10 and IL-6 
      translation and expression but did not affect the LPS-induced TNFalpha production. 
      Both the mTOR pathway and the LPS-induced IL-6 production were down-regulated by 
      HTS pretreatment. CONCLUSIONS: The PI3k/Akt/mTOR cascade modulates LPS-induced 
      cytokines production differentially. IL-10 and IL-6 expression are both 
      up-regulated by activation of the mTOR pathway in response to LPS in PBMCs, while 
      TNFalpha is not controlled by the mTOR cascade. Meanwhile, pretreatment of PBMCs with 
      a HTS solution suppresses mTOR activity as well as LPS-induced IL-6, suggesting a 
      more central role for mTOR as a regulator of the immuno-inflammatory response.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Schaeffer, Valerie
AU  - Schaeffer V
AD  - Harborview Medical Center, University of Washington, Seattle, Washington 98109, 
      USA. valschae@u.washington.edu
FAU - Arbabi, Saman
AU  - Arbabi S
FAU - Garcia, Iris A
AU  - Garcia IA
FAU - Knoll, Megan L
AU  - Knoll ML
FAU - Cuschieri, Joseph
AU  - Cuschieri J
FAU - Bulger, Eileen M
AU  - Bulger EM
FAU - Maier, Ronald V
AU  - Maier RV
LA  - eng
GR  - R01 GM045873-09/GM/NIGMS NIH HHS/United States
GR  - T32 GM007037/GM/NIGMS NIH HHS/United States
GR  - T32 GM007037-24/GM/NIGMS NIH HHS/United States
GR  - R01 GM45813/GM/NIGMS NIH HHS/United States
GR  - T32 GM07037/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100609
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (IL10 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Saline Solution, Hypertonic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Anti-Bacterial Agents/pharmacology
MH  - Cell Cycle Proteins
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-10/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Monocytes/*drug effects/immunology/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphoproteins/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Saline Solution, Hypertonic/*pharmacology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/immunology/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3006012
MID - NIHMS207605
EDAT- 2010/09/11 06:00
MHDA- 2012/01/10 06:00
PMCR- 2012/12/01
CRDT- 2010/09/11 06:00
PHST- 2010/02/19 00:00 [received]
PHST- 2010/04/22 00:00 [revised]
PHST- 2010/05/13 00:00 [accepted]
PHST- 2010/09/11 06:00 [entrez]
PHST- 2010/09/11 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S0022-4804(10)00481-6 [pii]
AID - 10.1016/j.jss.2010.05.035 [doi]
PST - ppublish
SO  - J Surg Res. 2011 Dec;171(2):769-76. doi: 10.1016/j.jss.2010.05.035. Epub 2010 Jun 
      9.