PMID- 23081841
OWN - NLM
STAT- MEDLINE
DCOM- 20130423
LR  - 20211021
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 57
IP  - 3
DP  - 2013 Mar
TI  - beta-catenin regulates innate and adaptive immunity in mouse liver 
      ischemia-reperfusion injury.
PG  - 1203-14
LID - 10.1002/hep.26100 [doi]
AB  - Dendritic cells (DCs) are critical mediators of immune responses that integrate 
      signals from the innate immune system to orchestrate adaptive host immunity. This 
      study was designed to investigate the role and molecular mechanisms of 
      STAT3-induced beta-catenin in the regulation of DC function and inflammatory 
      responses in vitro and in vivo. STAT3 induction in lipopolysaccharide 
      (LPS)-stimulated mouse bone marrow-derived DCs (BMDCs) triggered beta-catenin 
      activation by way of GSK-3beta phosphorylation. The activation of beta-catenin 
      inhibited phosphatase and tensin homolog delete on chromosome 10 (PTEN) and 
      promoted the phosphoinositide 3-kinase (PI3K)/Akt pathway, which in turn 
      down-regulated DC maturation and function. In contrast, knockdown of beta-catenin 
      increased PTEN/TLR4 (Toll-like receptor 4), interferon regulatory factor-3 
      (IRF3), nuclear factor kappa B (NF-kappaB) activity, and proinflammatory cytokine 
      programs in response to LPS stimulation. In a mouse model of warm liver ischemia 
      and reperfusion injury (IRI), disruption of beta-catenin signaling increased the 
      hepatocellular damage, enhanced hepatic DC maturation/function, and PTEN/TLR4 
      local inflammation in vivo. CONCLUSION: These findings underscore the role of 
      beta-catenin to modulate DC maturation and function at the innate-adaptive 
      interface. Activation of beta-catenin triggered PI3K/Akt, which in turn inhibited 
      TLR4-driven inflammatory response in a negative feedback regulatory mechanism. By 
      identifying the molecular pathways by which beta-catenin regulates DC function, our 
      findings provide the rationale for novel therapeutic approaches to manage local 
      inflammation and injury in IR-stressed liver.
CI  - Copyright (c) 2012 American Association for the Study of Liver Diseases.
FAU - Ke, Bibo
AU  - Ke B
AD  - Dumont-UCLA Transplant Center, Department of Surgery, Division of Liver and 
      Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, 
      CA 90095, USA.
FAU - Shen, Xiu-Da
AU  - Shen XD
FAU - Kamo, Naoko
AU  - Kamo N
FAU - Ji, Haofeng
AU  - Ji H
FAU - Yue, Shi
AU  - Yue S
FAU - Gao, Feng
AU  - Gao F
FAU - Busuttil, Ronald W
AU  - Busuttil RW
FAU - Kupiec-Weglinski, Jerzy W
AU  - Kupiec-Weglinski JW
LA  - eng
GR  - R01 DK062357/DK/NIDDK NIH HHS/United States
GR  - DK 062357/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130207
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (beta Catenin)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Adaptive Immunity/*physiology
MH  - Animals
MH  - Apoptosis/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Disease Models, Animal
MH  - Immunity, Innate/*physiology
MH  - Liver Diseases/*immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PTEN Phosphohydrolase/immunology/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Reperfusion Injury/*immunology/metabolism
MH  - STAT3 Transcription Factor/immunology/metabolism
MH  - Signal Transduction/immunology
MH  - Toll-Like Receptor 4/immunology/metabolism
MH  - beta Catenin/genetics/*immunology/metabolism
PMC - PMC3594407
MID - NIHMS415061
EDAT- 2012/10/20 06:00
MHDA- 2013/04/24 06:00
PMCR- 2014/03/01
CRDT- 2012/10/20 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2012/10/01 00:00 [accepted]
PHST- 2012/10/20 06:00 [entrez]
PHST- 2012/10/20 06:00 [pubmed]
PHST- 2013/04/24 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 10.1002/hep.26100 [doi]
PST - ppublish
SO  - Hepatology. 2013 Mar;57(3):1203-14. doi: 10.1002/hep.26100. Epub 2013 Feb 7.