title: The Effect of Elevated Intra-Abdominal Pressure on TLR4 Signaling in Intestinal Mucosa and on Intestinal Bacterial Translocation in a Rat.
abstract: BACKGROUND
  Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes. Rats were sacrificed 24 hours later. BT to mesenteric lymph nodes, liver, portal vein blood, and peripheral blood was determined at sacrifice. TLR4-related gene and protein expression (TLR-4; myeloid differentiation factor 88 [Myd88] and TNF-α receptor-associated factor 6 [TRAF6]) expression were determined using real-time PCR, western blotting, and immunohistochemistry.
  
  
  RESULTS
  Thirty percent of sham rats developed BT in the mesenteric lymph nodes (level I) and 20% of control rats developed BT in the liver and portal vein (level II). abdominal compartment syndrome (ACS) rats demonstrated an 80% BT in the lymph nodes (Level I) and 40% BT in the liver and portal vein (Level II). Elevated BT was accompanied by a significant increase in TLR-4 immunostaining in jejunum (51%) and ileum (35.9%), and in a number of TRAF6-positive cells in jejunum (2.1%) and ileum (24.01%) compared to control animals. ACS rats demonstrated a significant increase in TLR4 and MYD88 protein levels compared to control animals.
  
  
  CONCLUSIONS
  Twenty-four hours after the induction of elevated IAP in a rat model, increased BT rates were associated with increased TLR4 signaling in intestinal mucosa.
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .|3 Department of Surgery, Bnai Zion Medical Center , Haifa, Israel .
authors.forename: Adam
authors.initials: A
authors.lastname: Strier
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .
authors.forename: Dragan
authors.initials: D
authors.lastname: Kravarusic
authors.affiliation: 4 Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan , Ann Arbor, Michigan.
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .
authors.forename: Isaac
authors.initials: I
authors.lastname: Srugo
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .
authors.forename: Nir
authors.initials: N
authors.lastname: Bitterman
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .
authors.forename: Tatiana
authors.initials: T
authors.lastname: Dorfman
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pollak
authors.affiliation: 3 Department of Surgery, Bnai Zion Medical Center , Haifa, Israel .
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Matter
authors.affiliation: 1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Laboratory of Intestinal Adaptation and Recovery, Haifa, Israel .|2 Department of Pediatric Surgery, Bnai Zion Medical Center , Haifa, Israel .
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D015153:Blotting, Western; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D059325:Intra-Abdominal Hypertension / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: TNF-α receptor-associated factor 6; bacterial translocation; intestine; intraabdominal pressure; myeloid differentiation factor 88; toll-like receptor 4