PMID- 26620228
OWN - NLM
STAT- MEDLINE
DCOM- 20160607
LR  - 20180923
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 470
IP  - 1
DP  - 2016 Jan 29
TI  - LYATK1 potently inhibits LPS-mediated pro-inflammatory response.
PG  - 1-8
LID - S0006-291X(15)30959-1 [pii]
LID - 10.1016/j.bbrc.2015.11.090 [doi]
AB  - Lipopolysaccharide (LPS)-primed monocytes/macrophages produce pro-inflammatory 
      cytokines, which could lead to endotoxin shock. TGF-beta-activated kinase1 (TAK1) 
      activation is involved in the process. In the current study, we studied the 
      potential effect of a selective TAK1 inhibitor, LYTAK1, on LPS-stimulated 
      response both in vitro and in vivo. We demonstrated that LYTAK1 inhibited 
      LPS-induced mRNA expression and production of several pro-inflammatory cytokines 
      [interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6)] 
      in RAW 264.7 macrophages. LYTAK1's activity was almost nullified with TAK1 
      shRNA-knockdown. Meanwhile, in both primary mouse bone marrow derived macrophages 
      (BMDMs) and human peripheral blood mononuclear cells (PBMCs), LPS-induced 
      pro-inflammatory cytokine production was again attenuated with LYTAK1 
      co-treatment. Molecularly, LYTAK1 dramatically inhibited LPS-induced TAK1-nuclear 
      factor kappa B (NFkappaB) and mitogen-activated protein kinase (Erk, Jnk and p38) 
      activation in RAW 264.7 cells, mouse BMDMs and human PBMCs. In vivo, oral 
      administration of LYTAK1 inhibited LPS-induced activation of TAK1-NFkappaB-p38 in 
      ex-vivo cultured PBMCs, and cytokine production and endotoxin shock in mice. 
      Together, these results demonstrate that LYTAK1 inhibits LPS-induced production 
      of several pro-inflammatory cytokines and endotoxin shock probably through 
      blocking TAK1-regulated signalings.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Xi, Feng
AU  - Xi F
AD  - Department of Intensive Care Unit, Taixing People(')s Hospital, Taixing, Jiangsu 
      Province, 225400, China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, China.
FAU - Wang, Xiujuan
AU  - Wang X
AD  - Department of Intensive Care Unit, Taixing People(')s Hospital, Taixing, Jiangsu 
      Province, 225400, China.
FAU - Kong, Wei
AU  - Kong W
AD  - Department of Intensive Care Unit, Taixing People(')s Hospital, Taixing, Jiangsu 
      Province, 225400, China.
FAU - Zhao, Feng
AU  - Zhao F
AD  - Department of Intensive Care Unit, Taixing People(')s Hospital, Taixing, Jiangsu 
      Province, 225400, China. Electronic address: taixingzhaofeng163@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151124
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cytokines/*immunology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Immunity, Cellular/drug effects/immunology
MH  - Leukocytes, Mononuclear/drug effects/*immunology
MH  - Lipopolysaccharides
MH  - MAP Kinase Kinase Kinases/*antagonists & inhibitors
MH  - Macrophages/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Kinase Inhibitors/*administration & dosage
MH  - RAW 264.7 Cells
MH  - Shock, Septic/chemically induced/*immunology/*prevention & control
OTO - NOTNLM
OT  - LPS
OT  - LYTAK1
OT  - Monocytes/macrophages and inflammation
OT  - TAK1 signalings
EDAT- 2015/12/02 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/12/02 06:00
PHST- 2015/11/17 00:00 [received]
PHST- 2015/11/20 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - S0006-291X(15)30959-1 [pii]
AID - 10.1016/j.bbrc.2015.11.090 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Jan 29;470(1):1-8. doi: 
      10.1016/j.bbrc.2015.11.090. Epub 2015 Nov 24.