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Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
Published on: January 5, 2017
Hypertonic saline reduces neutrophil-epithelial interactions in vitro and gut tissue damage in a mouse model of
Wolfgang Tillinger1, Declan F McCole, Stephen J Keely
1Division of Gastroenterology, Department of Medicine, University of California, San Diego, Mailcode 0063, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Abstract:
Transepithelial migration of polymorphonuclear neutrophils (PMN) plays a crucial role in inflammatory conditions of the intestine, such as inflammatory bowel diseases. Hypertonic saline (HS) exerts various inhibitory effects on PMN function. We hypothesized that HS could inhibit transepithelial migration of PMN and thereby prevent inflammatory events in experimental colitis. Isolated human PMN were treated with HS (40 mM), and their transmigration across a monolayer of T84 epithelial cells was induced by N-formyl-methionyl-leucyl-phenylalanine. Monolayer disruption was assessed by monitoring changes in transepithelial conductance in an Ussing chamber. Colitis in mice was induced by oral administration of dextran sulfate sodium (DSS). Animals were treated with 4 or 8 ml/kg of 7.5% saline intraperitoneally two times daily for 7 days. Controls received equivalent volumes of normal saline (NS, n = 6) or no intraperitoneal treatment (DSS, n = 12). The severity of inflammation was evaluated based on disease activity index and histology score. HS treatment of PMN in vitro significantly reduced cell migration and the disruption of T84 monolayers compared with untreated control cells (n = 5, P < 0.05). This effect of HS was dose dependent. HS treatment in vivo also reduced colitis-induced gut tissue damage, as indicated by an improved histology score compared with the NS and DSS groups. We conclude that HS inhibits transepithelial migration of PMN in vitro and gut tissue damage in vivo in a mouse model of colitis. Thus HS may have clinical value to reduce PMN-mediated intestinal damage.
Insights
Hypertonic saline (HS) inhibits polymorphonuclear neutrophil (PMN) migration across intestinal cells and reduces gut tissue damage in experimental colitis. This suggests HS may be valuable for treating PMN-mediated intestinal inflammation.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Transepithelial migration of polymorphonuclear neutrophils (PMN) is critical in intestinal inflammatory diseases like inflammatory bowel disease.
- Hypertonic saline (HS) is known to inhibit various PMN functions.
Purpose of the Study:
- To investigate the hypothesis that HS can inhibit PMN transepithelial migration and prevent inflammatory events in experimental colitis.
- To evaluate the therapeutic potential of HS in managing colitis.
Main Methods:
- In vitro: Human PMN were treated with HS and their transmigration across T84 epithelial cell monolayers was assessed.
- In vitro: Monolayer disruption was measured by transepithelial conductance changes in an Ussing chamber.
- In vivo: Colitis was induced in mice using dextran sulfate sodium (DSS) and animals were treated with HS or normal saline (NS).
- In vivo: Inflammation severity was evaluated using disease activity index and histology scores.
Main Results:
- HS significantly reduced PMN migration and T84 monolayer disruption in vitro, demonstrating a dose-dependent effect.
- In vivo, HS treatment attenuated DSS-induced colitis, leading to improved histology scores compared to NS and DSS control groups.
- HS effectively inhibited PMN transmigration and reduced gut tissue damage in experimental models.
Conclusions:
- Hypertonic saline inhibits PMN transepithelial migration in vitro and reduces gut tissue damage in a mouse model of colitis.
- HS demonstrates potential clinical value in mitigating PMN-mediated intestinal damage and inflammation.
