Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation
AbstractUlcerative 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
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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.
Eissa N, Hussein H, Mesgna R, Bonin S, Hendy GN, Metz-Boutigue M-H, Bernstein CN, Ghia J-E. Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation. Vaccines. 2018; 6(4):67.Chicago/Turabian Style
Eissa, Nour; Hussein, Hayam; Mesgna, Ruth; Bonin, Sandra; Hendy, Geoffrey N.; Metz-Boutigue, Marie-Hélène; Bernstein, Charles N.; Ghia, Jean-Eric. 2018. "Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation." Vaccines 6, no. 4: 67.
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