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
ARTICLE HIGHLIGHTS
Research background

Ulcerative colitis (UC) is a disorder in which the gastrointestinal tract becomes ulcerated and inflamed. Although treatments and therapeutic strategies are evolving quickly, treatments are still inadequate for a substantial percentage of those with active UC, and some therapies may have serious adverse side effects. Therefore, UC needs new therapeutic approaches associated with higher efficacy and limited side effects. In UC, there is an overactivation of innate immune cells such as macrophages and dendritic cells (DCs). Recently, in the context of UC and experimental colitis, new data highlighted an essential anti-inflammatory role of chromofungin (CHR), a chromogranin-A derived peptide, on peritoneal macrophages.

Research motivation

To evaluate CHR's effects on different DCs at various immune compartments and to define a potential intracellular pathway implicated.

Research objectives

To investigate the association between CHR treatment and DCs-related markers in colitis.

Research methods

Participants with active UC and a model of acute UC-like colitis using dextran sulphate sodium were used. We used cell culture and quantitative reverse transcription-polymerase chain reaction to analyze the relative expression levels of CD11c, CD80, CD86, interleukin (IL)-6 and IL-12p40 within the colonic samples, mesenteric lymph nodes and the spleen.

Research results

In a preclinical setting, CHR treatment the expression of CD11c, CD40, CD80, CD86 and IL-12p40 in the inflamed colonic mucosa and CD11c, CD80, CD86, IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen. In addition, CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+ cells and decreased NF-κB expression in the colon and splenic CD11c+ cells. In vitro, CHR decreased CD40, CD80, CD86, IL-6, and IL-12p40 expression in naïve bone marrow-derived CD11c+ DC stimulated lipopolysaccharide. Using a pharmacological approach, we demonstrated the impact of CHR on the NF-κB pathway. In a clinical setting, in patients with active UC, CHR level was reduced and showed a negative linear relationship with CD11c and CD86.

Research conclusions

CHR has protective properties against intestinal inflammation, potentially through the regulation of DC-related markers and CD11c+ cells.

Research perspectives

Although we have demonstrated that CHR may have a potential therapeutic interest, additional markers and detailed mechanisms of action need to be determined in a large sample.