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: Adam Strier, Dragan Kravarusic, Arnold G Coran, Isaac Srugo, Nir Bitterman, Tatiana Dorfman, Yulia Pollak, Ibrahim Matter, Igor Sukhotnik
• Journal: Journal of laparoendoscopic & advanced surgical techniques. Part A (J Laparoendosc Adv Surg Tech A) Vol. 27 Issue 2 Pg. 211-216 (Feb 2017) ISSN: 1557-9034 [Electronic] United States
• PMID: 27875107 (Publication Type: Journal Article)

Chemical References

• Tlr4 protein, rat
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Bacterial Translocation
• Blotting, Western
• Immunohistochemistry
• Intestinal Mucosa (metabolism)
• Intestines (microbiology)
• Intra-Abdominal Hypertension (complications, metabolism, microbiology)
• Male
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)