PMID- 31629474
OWN - NLM
STAT- MEDLINE
DCOM- 20200706
LR  - 20200706
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 521
IP  - 1
DP  - 2020 Jan 1
TI  - 3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses 
      FcepsilonRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt 
      signaling.
PG  - 72-76
LID - S0006-291X(19)31968-0 [pii]
LID - 10.1016/j.bbrc.2019.10.075 [doi]
AB  - Mast cells express high-affinity IgE receptor (FcepsilonRI) on their surface, 
      cross-linking of which leads to the immediate release of proinflammatory 
      mediators such as histamine but also late-phase cytokine secretion, which are 
      central to the pathogenesis of allergic diseases. Despite the growing evidences 
      that mammalian target of rapamycin (mTOR) plays important roles in the immune 
      system, it is still unclear how mTOR signaling regulates mast cell function. In 
      this study, we investigated the effects of 3-benzyl-5-((2-nitrophenoxy) 
      methyl)-dihydrofuran-2(3H)-one (3BDO) as an mTOR agonist on FcepsilonRI-mediated 
      allergic responses of mast cells. Our data showed that administration of 3BDO 
      decreased beta-hexosaminidase, interleukin 6 (IL-6), and tumor necrosis factor-alpha 
      (TNF-alpha) release in murine bone marrow-derived mast cells (BMMCs) after FcepsilonRI 
      cross-linking, which was associated with an increase in mTOR complex 1 (mTORC1) 
      signaling but a decrease in activation of Erk1/2, Jnk, and mTORC2-Akt. In 
      addition, we found that a specific Akt agonist, SC79, is able to fully restore 
      the decrease of beta-hexosaminidase release in 3BDO-treated BMMCs but has no effect 
      on IL-6 release in these cells, suggesting that 3BDO negatively regulates 
      FcepsilonRI-mediated degranulation and cytokine release through differential mechanisms 
      in mast cells. The present data demonstrate that proper activation of mTORC1 is 
      crucial for mast cell effector function, suggesting the applicability of the 
      mTORC1 activator as a useful therapeutic agent in mast cell-related diseases.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Rakhmanova, Valeriya
AU  - Rakhmanova V
AD  - Department of Microbiology, Inha University School of Medicine, Incheon, 22212, 
      South Korea.
FAU - Park, Sukyoung
AU  - Park S
AD  - Department of Microbiology, Inha University School of Medicine, Incheon, 22212, 
      South Korea.
FAU - Lee, Sungwook
AU  - Lee S
AD  - Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea.
FAU - Kim, Young Hyo
AU  - Kim YH
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School 
      of Medicine, Incheon, 22212, South Korea.
FAU - Shin, Jinwook
AU  - Shin J
AD  - Department of Microbiology, Inha University School of Medicine, Incheon, 22212, 
      South Korea. Electronic address: shin001@inha.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191016
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one)
RN  - 0 (Receptors, IgE)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - OL659KIY4X (4-Butyrolactone)
SB  - IM
MH  - 4-Butyrolactone/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Cell Degranulation/*drug effects
MH  - Mast Cells/*drug effects/immunology
MH  - Mechanistic Target of Rapamycin Complex 2/*antagonists & inhibitors/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/immunology
MH  - Receptors, IgE/*antagonists & inhibitors/immunology
MH  - Signal Transduction/drug effects/immunology
OTO - NOTNLM
OT  - 3BDO
OT  - Activation
OT  - Akt
OT  - Mast cells
OT  - mTOR
EDAT- 2019/10/21 06:00
MHDA- 2020/07/07 06:00
CRDT- 2019/10/21 06:00
PHST- 2019/09/14 00:00 [received]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/10/21 06:00 [pubmed]
PHST- 2020/07/07 06:00 [medline]
PHST- 2019/10/21 06:00 [entrez]
AID - S0006-291X(19)31968-0 [pii]
AID - 10.1016/j.bbrc.2019.10.075 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Jan 1;521(1):72-76. doi: 
      10.1016/j.bbrc.2019.10.075. Epub 2019 Oct 16.