Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2021; 27(47): 8138-8155
Published online Dec 21, 2021. doi: 10.3748/wjg.v27.i47.8138
Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions
Kunal Kapoor, Nour Eissa, Diane Tshikudi, Charles N Bernstein, Jean-Eric Ghia
Kunal Kapoor, Nour Eissa, Diane Tshikudi, Jean-Eric Ghia, Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada
Nour Eissa, Jean-Eric Ghia, Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg R3E0T5, MB, Canada
Nour Eissa, Charles N Bernstein, Jean-Eric Ghia, Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg R3E0T5, MB, Canada
Nour Eissa, Charles N Bernstein, Jean-Eric Ghia, University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg R3E0T5, MB, Canada
Author contributions: Kapoor K, Eissa N and Ghia JE conceived and designed the experiments; Bernstein CN collected the human tissue and collated the human data; Kapoor K and Eissa N performed the experiments; Kapoor K, Eissa N, Ghia JE and Bernstein CN analyzed the data; Kapoor K, Eissa N, Tshikudi D and Ghia JE wrote and assembled the paper; all authors have read and approved the final manuscript.
Supported by Crohn's and Colitis Canada, No. P46601; Canadian Foundation for Innovation, No. P39902; Children's Hospital Research Institute of Manitoba, No. P45040; Natural Sciences and Engineering Research Council, No. P41224; and Manitoba Health Research Council, No. P41118 (to Ghia JE).
Institutional review board statement: The study was reviewed and approved by the University of Manitoba Research Ethics Board [HS14878 (E)].
Institutional animal care and use committee statement: All the experiments were conducted under protocols #15-010 and #19-014, approved by the University of Manitoba Ethics Committee under Canadian animal research guidelines.
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.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jean-Eric Ghia, AGAF, MSc, PhD, Associate Professor, Director, Department of Immunology, University of Manitoba, 750 McDermot Ave, Apotex 431, Winnipeg R3E0T5, MB, Canada. jean-eric.ghia@umanitoba.ca
Received: March 12, 2021
Peer-review started: March 12, 2021
First decision: May 1, 2021
Revised: May 12, 2021
Accepted: December 7, 2021
Article in press: December 7, 2021
Published online: December 21, 2021
Processing time: 279 Days and 13.4 Hours
Abstract
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.

Keywords: Chromofungin; Chromogranin-A; Colitis; Cytokines; Dendritic cells; Gut hormones

Core Tip: Ulcerative colitis (UC) is characterized by a colonic decrease of chromofungin (CHR: chromogranin-A 47-66) and a dysregulation of CD11c+ dendritic cells (DC). Using a UC-like model (dextran sulphate sodium) and biopsies collected from UC patients, we demonstrated a protective effect of CHR via the regulation of DC-related markers and CD11c+ cells at the colonic, mesenteric lymph node and spleen levels, through a potential effect via the NF-κB pathway. In patients with active UC, CHR level showed a negative linear relationship with CD11c+ marker. CHR could be a potential therapy of UC, but larger samples and additional experiments are needed.