Protection of intestinal occludin tight junction protein by dietary gangliosides in lipopolysaccharide-induced acute inflammation.

Abstract

OBJECTIVES:

Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation.

MATERIALS AND METHODS:

Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined.

RESULTS:

Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS.

CONCLUSIONS:

Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.

• Authors: Eek J Park, Alan B R Thomson, Michael T Clandinin
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 50 Issue 3 Pg. 321-8 (Mar 2010) ISSN: 1536-4801 [Electronic] United States
• PMID: 20118807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Dietary Fats
• Gangliosides
• Lipopolysaccharides
• Membrane Proteins
• OCLN protein, human
• Occludin
• Ocln protein, rat
• Interleukin-10
• Nitric Oxide
• Nitric Oxide Synthase Type II

Topics

• Acute Disease
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Membrane Permeability (drug effects)
• Dietary Fats (administration & dosage)
• Gangliosides (pharmacology)
• Inflammation (chemically induced, drug therapy, metabolism)
• Interleukin-10 (blood, metabolism)
• Intestinal Absorption
• Intestinal Mucosa (drug effects, metabolism)
• Lipopolysaccharides
• Male
• Membrane Proteins (metabolism)
• Nitric Oxide (blood, metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Occludin
• Rats
• Rats, Sprague-Dawley
• Tight Junctions (drug effects, metabolism)