Alanyl‐glutamine Protects Against Damage Induced by Enteroaggregative Escherichia coli Strains in Intestinal Cells

• Published in: Journal of pediatric gastroenterology and nutrition Vol. 68; no. 2; pp. 190 - 198
• Main Authors: Prata, Mara M.G., Cavalcante, Paloma A., Silva, Antonio V. Alves, Medeiros, Pedro H.Q.S., Assis Júnior, Eudmar M., Reyes, Mayra A.V., Quetz, Josiane da S., Clementino, Marco A.F., Ribeiro, Samilly A., Lima, Ila F.N., Lima‐Junior, Roberto C.P., Havt, Alexandre, Guerrant, Richard L., Lima, Aldo A.M.
• Format: Journal Article
• Language: English
• Published: United States by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology 01-02-2019
• Subjects: alanyl‐glutamine; cell death; Cell Survival - drug effects; Chemokine CXCL1 - metabolism; Child; Dietary Supplements; Dipeptides - pharmacology; enteroaggregative Escherichia coli; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Escherichia coli - metabolism; Escherichia coli Infections - metabolism; Escherichia coli Infections - microbiology; Escherichia coli Infections - therapy; Humans; intestinal epithelial cell; Intestinal Mucosa - cytology; Intestinal Mucosa - microbiology; Protective Agents - pharmacology
• ISSN: 0277-2116; 1536-4801
• DOI: 10.1097/MPG.0000000000002152

ABSTRACT
Background:
Enteroaggregative Escherichia coli (EAEC) is an important pathogen causing enteric infections worldwide. This pathotype is linked to malnutrition in children from developing countries. Alanyl‐glutamine (Ala‐Gln) is an immune modulator nutrient that acts during intestinal damage and/or inflammation. This study investigated the effect of EAEC infection and Ala‐Gln on cell viability, cell death, and inflammation of intestinal epithelium cells (IEC‐6).
Methods:
Cells were infected with an EAEC prototype 042 strain, an EAEC wild‐type strain isolated from a Brazilian malnourished child, and a commensal E coli HS. Gene transcription and protein levels of caspases‐3, ‐8, and ‐9 and cytokine‐induced neutrophil chemoattractant 1 (CINC‐1/CXCL1) were evaluated using RT‐qPCR, western blot analysis, and ELISA.
Results:
Infections with both EAEC strains decreased cell viability and induced apoptosis and necrosis after 24 hours. Ala‐Gln supplementation increased cell proliferation and reduced cell death in infected cells. Likewise, EAEC strain 042 significantly increased the transcript levels of caspases‐3, ‐8, and ‐9 when compared to the control group, and Ala‐Gln treatment reversed this effect. Furthermore, EAEC induced CXCL1 protein levels, which were also reduced by Ala‐Gln supplementation.
Conclusion:
These findings suggest that EAEC infection promotes apoptosis, necrosis, and intestinal inflammation with involvement of caspases. Supplementation of Ala‐Gln inhibits cell death, increases cell proliferation, attenuates mediators associated with cell death, and inflammatory pathways in infected cells.