Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2022; 28(40): 5865-5880
Published online Oct 28, 2022. doi: 10.3748/wjg.v28.i40.5865
Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling
Si-Yi Wei, Tian-Tian Wu, Jia-Qi Huang, Zeng-Ping Kang, Meng-Xue Wang, You-Bao Zhong, Wei Ge, Bu-Gao Zhou, Hai-Mei Zhao, Hai-Yan Wang, Duan-Yong Liu
Si-Yi Wei, Tian-Tian Wu, Jia-Qi Huang, Zeng-Ping Kang, Meng-Xue Wang, Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
You-Bao Zhong, Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Wei Ge, Affiliated Hospital, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Bu-Gao Zhou, Hai-Mei Zhao, Hai-Yan Wang, Duan-Yong Liu, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Author contributions: Wei SY and Wu TT contributed equally to this work and should be regarded as co-first authors; Huang JQ, Zhong YB, Kang ZP, Wang MX, Zhou BG, Zhao HM, and Ge W performed the experiments; Liu DY and Wang HY contributed reagents/materials/analytical tools; Liu DY and Zhong YB analyzed the data; Wei SY, Wu TT, and Liu DY wrote the paper; Liu DY and Wang HY conceived and designed the experiments.
Supported by the National Natural Science Foundation of China, No. 81760808; and Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, No. CXTD22008.
Institutional animal care and use committee statement: The study was reviewed and approved by the Jiangxi University of Chinese Medicine Animal Care and Use Committee and were performed in accordance with its prescribed guidelines (Approval No. JZLLSC2021-196).
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
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: Duan-Yong Liu, PhD, Director, Full Professor, Professor, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, No. 1688 Meiling Road, Nanchang 330004, Jiangxi Province, China. liuduanyong@163.com
Received: July 25, 2022
Peer-review started: July 25, 2022
First decision: August 19, 2022
Revised: August 20, 2022
Accepted: October 13, 2022
Article in press: October 13, 2022
Published online: October 28, 2022
Abstract
BACKGROUND

Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD.

AIM

To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.

METHODS

Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1β, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins.

RESULTS

After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1β, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice.

CONCLUSION

Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Keywords: Curcumin, Experimental colitis, Memory B cell, Bcl-6, BLNK

Core Tip: As the precursor of B cells, the activation of memory B cells can trigger the activation of B cells, thus producing numerous inducible B cells and tolerant B cells, whose dysfunction can easily result in inflammatory bowel disease (IBD). Also, the disorder of humoral immune function mediated by memory B cells has a critical position in the pathogenesis of IBD. As an immune suppressant, curcumin (Cur) has a therapeutic role in treating many immune diseases, such as IBD and rheumatoid arthritis. Meanwhile, it has proven efficacy in experimental colitis mice and patients with ulcerative colitis (UC), while the disturbances in memory B cells have been observed in IBD. However, few studies have explored whether Cur treatment of colitis is closely related to memory B cells. In the present research, our results indicated that Cur effectively alleviated DSS-induced UC in mice via a potential mechanism involving memory B cells and the Bcl-6-Syk-BLNK signaling pathway.