Download the full-sized PDF
Permanent link (DOI): https://doi.org/10.7939/R3DQ2K
This file is in the following communities:
|Graduate Studies and Research, Faculty of|
This file is in the following collections:
|Theses and Dissertations|
Gangliosides and Inflammatory Bowel Disease Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Clandinin, Tom (Dept. of Agricultural, Food and Nutritional Science
- Examining committee member and department
Mazurak, Vera (Dept. of Agricultural, Food and Nutritional Science)
Reimer, Raylene (Dept. of Biochemistry and Molecular Biology), University of Calgary
Thomson, Alan (Divission of Gastroenterology), University of Western Ontario
Field, Catherine (Dept. of Agicultural, Food and Nutritional Science)
Department of Agricultural, Food, and Nutritional Science
Nutrition and Metabolism
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
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.
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
- Citation for previous publication
- Date Uploaded
- Date Modified
- Audit Status
- Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 1607350
Last modified: 2015:10:12 10:58:34-06:00
Original checksum: cfcc70098fb7a8c5043c8c41bb17e950
Well formed: true
Page count: 164
File language: en-US