Gangliosides and Inflammatory Bowel Disease

  • Author / Creator
    Li, Qun
  • Inflammatory bowel disease (IBD) involves chronic inflammation of all or part of the digestive tract. IBD primarily includes ulcerative colitis and Crohn disease. Gangliosides are negatively charged glycosphingolipids that consist of a hydrophobic ceramide and a hydrophilic oligosaccharide chain bearing one or more sialic acid. Both animal and human cell studies suggest that gangliosides have anti-inflammatory effects by decreasing tumor necrosis factor- α (TNF-α), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). The objective of this study was to evaluate Lipopolysaccharide (LPS) stimulated and dextran sulfate sodium (DSS) induced inflammation of Caco-2 cells as a model of IBD and to investigate the effect of ganglioside supplementation. Ganglioside was extracted from milk powder and used as the ganglioside supplement in cell cultures. Intestinal integrity was examined by electron microscopy. Epithelial barrier function was examined by measuring trans epithelial electric resistance (TEER). HBD-2, IL-23, NF-kB and sPLA2 (secretory phospholipase A2) was determined by ELISA methods. apoB 48 was measured by western blot. Both LPS and DSS treatment result in higher HBD-2 level, activation of NF-kB P65 and secretion of sPLA2 in the basolateral medium, while decreased intestinal barrier function ( P≤0.05). In LPS induced IBD Caco-2 model, the research demonstrates that ganglioside incubation decreases pro-inflammatory HBD-2 and IL-23 levels ( P≤0.05) by improving barrier function and inhibiting NF-kB activation ( P≤0.05) and independent of sPLA2 level. Ganglioside also increases the secretion of apoB 48 after LPS stimulation ( P≤0.05). This research demonstrates that in DSS induced IBD Caco-2 model ganglioside incubation decreases the secretion of sPLA2 in the basolateral medium after DSS treatment ( P≤0.05). Ganglioside incubation protected the integrity of cellular phospholipids, including phosphatidylethanolamine (PE) and phosphatidylinositol (PI). In summary, the present study indicates that both LPS and DSS induced Caco-2 cells are useful models to study IBD. Ganglioside incubation in cell culture may have promising potential beneficial effects on IBD by decreasing inflammatory signaling and improving intestinal integrity and epithelial barrier function. The anti-inflammatory effect observed is related to sPLA2 and NF-kB activation depends on the pathogenesis of IBD.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Agricultural, Food, and Nutritional Science
  • Specialization
    • Nutrition and Metabolism
  • Supervisor / co-supervisor and their department(s)
    • Clandinin, Tom (Dept. of Agricultural, Food and Nutritional Science
  • Examining committee members and their departments
    • Field, Catherine (Dept. of Agicultural, Food and Nutritional Science)
    • Thomson, Alan (Divission of Gastroenterology), University of Western Ontario
    • Reimer, Raylene (Dept. of Biochemistry and Molecular Biology), University of Calgary
    • Mazurak, Vera (Dept. of Agricultural, Food and Nutritional Science)