PMID- 21392794
OWN - NLM
STAT- MEDLINE
DCOM- 20120706
LR  - 20120410
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 174
IP  - 2
DP  - 2012 May 15
TI  - TLR4 mediates lung injury and inflammation in intestinal ischemia-reperfusion.
PG  - 326-33
LID - 10.1016/j.jss.2010.12.005 [doi]
AB  - BACKGROUND: Splanchnic ischemia is common in critically ill patients, and it can 
      result in injury not only of the intestine but also in distant organs, 
      particularly in the lung. Local inflammatory changes play a pivotal role in the 
      development of acute lung injury after intestinal ischemia, but the underlying 
      molecular mechanisms are not fully understood. We sought to examine the role of 
      Toll-like receptor 4 (TLR4) in the mouse model of intestinal ischemia-reperfusion 
      (I/R)-induced lung injury and inflammation. MATERIALS AND METHODS: Adult male 
      TLR4 mutant (C3H/HeJ) mice and TLR4 wild-type (WT) (C3H/HeOuJ) mice were 
      subjected to 40 min of intestinal ischemia by clamping the superior mesenteric 
      artery followed by 6 h of reperfusion. Lung histology was assessed and parameters 
      of pulmonary microvascular permeability, inflammatory cytokine expression, and 
      neutrophil infiltration were measured. Activation of mitogen-activated protein 
      kinases (MAPKs) and the transcription factors nuclear factor kappaB (NF-kappaB) and 
      activator protein-1 (AP-1) in the lungs were also detected. RESULTS: After 
      intestinal I/R, lungs from TLR4 mutant mice demonstrated a significantly lower 
      histological injury, a marked reduction of epithelial apoptosis associated with 
      the decreased level of cleaved caspase-3 and the increased ratio of Bcl-xL to Bax 
      proteins, and a large reduction in pulmonary vascular permeability and 
      myeloperoxidase (MPO) activity in comparison with WT mice. TLR4 mutant mice also 
      displayed marked decreases in tumor necrosis factor-alpha (TNF-alpha), interleukin-6 
      (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory 
      protein-2 (MIP-2) expression. Following intestinal I/R, phosporylation of p38 
      MAPK and activation of NF-kappaB and AP-1 were significantly inhibited in lung tissue 
      from TLR4 mutant mice compared with WT controls. CONCLUSIONS: These data suggest 
      that TLR4 plays an important role in the pathogenesis of intestinal I/R-induced 
      acute lung injury and inflammation and that p38 kinase and NF-kappaB may be involved 
      in TLR4 signaling-mediated lung inflammatory processes during intestinal I/R.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Ben, Dao-Feng
AU  - Ben DF
AD  - Institute of Burn Surgery and Burn Center, Changhai Hospital, Second Military 
      Medical University, Shanghai, China.
FAU - Yu, Xi-Ya
AU  - Yu XY
FAU - Ji, Guang-Yu
AU  - Ji GY
FAU - Zheng, De-Yi
AU  - Zheng DY
FAU - Lv, Kai-Yang
AU  - Lv KY
FAU - Ma, Bing
AU  - Ma B
FAU - Xia, Zhao-Fan
AU  - Xia ZF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110105
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transcription Factor AP-1)
RN  - 147257-52-1 (Nfkb1 protein, mouse)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Lung Injury/etiology/*metabolism/pathology
MH  - Animals
MH  - Apoptosis
MH  - Capillary Permeability
MH  - Cytokines/metabolism
MH  - Enzyme Activation
MH  - Epithelial Cells/pathology
MH  - Intestines/*blood supply
MH  - Lung/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Neutrophil Infiltration
MH  - Reperfusion Injury/*complications/pathology
MH  - Toll-Like Receptor 4/*metabolism
MH  - Transcription Factor AP-1/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2011/03/12 06:00
MHDA- 2012/07/07 06:00
CRDT- 2011/03/12 06:00
PHST- 2010/08/30 00:00 [received]
PHST- 2010/11/16 00:00 [revised]
PHST- 2010/12/03 00:00 [accepted]
PHST- 2011/03/12 06:00 [entrez]
PHST- 2011/03/12 06:00 [pubmed]
PHST- 2012/07/07 06:00 [medline]
AID - S0022-4804(10)01868-8 [pii]
AID - 10.1016/j.jss.2010.12.005 [doi]
PST - ppublish
SO  - J Surg Res. 2012 May 15;174(2):326-33. doi: 10.1016/j.jss.2010.12.005. Epub 2011 
      Jan 5.