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Article Dans Une Revue Vaccines Année : 2018

Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation

Résumé

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. Keywords: chromogranin-A; colitis; host-defense peptides; inflammatory bowel diseases; innate immunity; intestinal permeability; mucosal drug action.
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Dates et versions

hal-03471679 , version 1 (08-12-2021)

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Nour Eissa, Hayam Hussein, Ruth Mesgna, Sandra Bonin, Geoffrey Hendy, et al.. Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation. Vaccines, 2018, 6 (4), pp.67. ⟨10.3390/vaccines6040067⟩. ⟨hal-03471679⟩
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