Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions.

Autor:	Kapoor K; Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada., Eissa N; Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada., Tshikudi D; Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada., Bernstein CN; Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg R3E0T5, MB, Canada., Ghia JE; Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada.
Jazyk:	angličtina
Zdroj:	World journal of gastroenterology [World J Gastroenterol] 2021 Dec 21; Vol. 27 (47), pp. 8138-8155.
DOI:	10.3748/wjg.v27.i47.8138
Abstrakt:	Background: Chromofungin (CHR: chromogranin-A 47-66) is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties. Ulcerative colitis (UC) is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c + cells. Aim: To investigate the association between CHR treatment and dendritic cells (DCs)-related markers in different immune compartments in colitis. Methods: A model of acute UC-like colitis using dextran sulphate sodium (DSS) was used in addition to biopsies collected from UC patients. Results: Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c, CD40, CD80, CD86 and interleukin (IL)-12p40 in the inflamed colonic mucosa and CD11c, CD80, CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen. Furthermore, CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c + cells and decreased NF-κB expression in the colon and of splenic CD11c + cells. In vitro, CHR decreased CD40, CD80, CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c + DCs stimulated with lipopolysaccharide. Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway. In patients with active UC, CHR level was reduced and showed a negative linear relationship with CD11c and CD86. Conclusion: CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c + cells. CHR could be a potential therapy of UC. Competing Interests: Conflict-of-interest statement: Bernstein CN has been on the advisory boards for Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Janssen Canada, Roche Canada, Sandoz Canada, Takeda Canada, Pfizer Canada and consulted to Takeda and Mylan Pharmaceuticals. He has received educational grants from Abbvie Canada, Pfizer Canada, Takeda Canada, Janssen Canada. He has been on speaker’s panel for Abbvie Canada, Medtronic Canada and Janssen Canada. The other authors declare that they have no conflicts of interest. (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)
Databáze:	MEDLINE
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