Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling

ARTICLE HIGHLIGHTS

Research background

Curcumin (Cur) has shown promising efficacy in experimental colitis mice and ulcerative colitis patients. Disturbance in memory B cells has been observed in various autoimmune diseases, including inflammatory bowel disease. However, few studies have explored whether Cur treatment of colitis is associated with memory B cells.

Research motivation

To the best of our knowledge, this is the first study to explore the mechanisms by which Cur regulates memory B cells in the treatment of experimental colitis.

Research objectives

To investigate whether Cur can alleviate experimental colitis induced by DSS through regulating memory B cells and Bcl-6-Syk-BLNK signaling.

Research methods

Cur (100 mg/kg/d) was intragastrically administered in mice with colitis induced by DSS for 14 consecutive days. The effect of Cur was evaluated by macroscopic and histological observation. The levels of memory B cell subgroups in mouse peripheral blood were detected by flow cytometry, and the levels of cytokines in colonic tissue homogenates were measured by using ELISA. The expression of Bcl-6, BLNK, and Syk was measured by Western blot analysis.

Research results

After mice were treated with Cur for 14 d, the body weight, colonic weight and length, colonic weight index, and histopathological injury were ameliorated. In colitis mice, the concentrations of IL-1β, IL-6, TNF-α, and IL-7A were significantly decreased, while the concentrations of anti-inflammatory cytokines IL-35 and IL-10 were obviously 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 observably decreased the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice.

Research conclusions

Cur could effectively alleviate DSS-induced colitis in mice, which is realized via a potential mechanism involving memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Research perspectives

In the present study, Cur effectively ameliorated the pathological colonic injury induced by DSS, which was achieved through a potential mechanism involving regulating the balance of memory B cells and activating the Bcl-6-Syk-BLNK signaling pathway.