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Vaccines 2018, 6(4), 67; https://doi.org/10.3390/vaccines6040067

Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation

1
Department of Immunology, Max Rady College of Manitoba, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
2
Internal Medicine section of Gastroenterology, Max Rady College of Manitoba, University of Manitoba, Winnipeg, MB R3A 1R9, Canada
3
IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB R3A 1R9, Canada
4
Children’s Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
5
Department of Parasitology and Animal Diseases, Veterinary Research Division, National Research Centre, Giza 12622, Egypt
6
Metabolic Disorders and Complications, McGill University Health Centre-Research Institute, Departments of Medicine, Physiology, and Human Genetics, McGill University, Montréal, QC H3A 0G4, Canada
7
INSERM U.1121, Faculté de Chirurgie Dentaire, Place de l’Hôpital, 67000 Strasbourg, France
*
Author to whom correspondence should be addressed.
Received: 28 June 2018 / Revised: 10 September 2018 / Accepted: 11 September 2018 / Published: 20 September 2018
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Abstract

Ulcerative colitis (UC) is characterized by aberrant regulation of tight junctions (TJ), signal transducer and activator of transcription 3 (STAT3), and interleukin (IL)-8/18, which lead to intestinal barrier defects. Catestatin (CST), an enterochromaffin-derived peptide, regulates immune communication and STAT-3 in the inflamed intestine. Here, we investigated the effects of CST during the development of inflammation using human biopsies from patients with active UC, human colonic epithelial cells (Caco2), and an experimental model of UC (dextran sulfate sodium [DSS]-colitis). In UC patients, the protein and mRNA level of CST was significantly decreased. Colonic expression of CST showed a strong positive linear relationship with TJ proteins and STAT3, and a strong negative correlation with IL-8 and IL-18. Intra-rectal administration of CST reduced the severity of experimental colitis, IL-18 colonic levels, maintained TJ proteins and enhanced the phosphorylation of STAT3. CST administration increased proliferation, viability, migration, TJ proteins, and p-STAT3 levels, and reduced IL-8 & IL-18 in LPS- & DSS-induced Caco2 cell epithelial injury, and the presence of STAT-3 inhibitor abolished the beneficial effect of CST. In inflammatory conditions, we conclude that CST could regulate intestinal mucosal dynamic via a potential STAT3-dependent pathway that needs to be further defined. Targeting CST in intestinal epithelial cells (IECs) should be a promising therapeutic approach such as when intestinal epithelial cell homeostasis is compromised in UC patients. View Full-Text
Keywords: chromogranin-A; colitis; host-defense peptides; inflammatory bowel diseases; innate immunity; intestinal permeability; mucosal drug action chromogranin-A; colitis; host-defense peptides; inflammatory bowel diseases; innate immunity; intestinal permeability; mucosal drug action
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Eissa, N.; Hussein, H.; Mesgna, R.; Bonin, S.; Hendy, G.N.; Metz-Boutigue, M.-H.; Bernstein, C.N.; Ghia, J.-E. Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation. Vaccines 2018, 6, 67.

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