N-(3', 4'-dimethoxycinnamonyl) anthranilic acid alleviated experimental colitis by inhibiting autoimmune response and inducing CD4+ CD25+ regulatory T cells production

Background and aim: Crohn's disease treatments available today are not quite satisfactory. N-(3', 4'-dimethoxycinnamonyl) anthranilic acid (3, 4-DAA) has been proved to be effective in many autoimmune diseases. Therefore, we investigated the immunologic function of 3, 4-DAA on trinitrobenzene sulfonic acid (TNBS) colitis and human Crohn's disease.

Methods: Mice with TNBS-induced colitis were treated with 3, 4-DAA or 1-methyl-tryptophan (1-MT). Colitis severity was assessed with clinical and histological scores. Cell proliferation, cytokine expression, and the percentage of CD4(+) CD25(+) T cells were measured in both mice and human samples.

Results: In mice treated with 3, 4-DAA, the clinical and histological scores were decreased (P < 0.05); the proliferation of mesenteric lymph nodes (MLNs) cells and lamina propria mononuclear cells (LPMCs) were inhibited (P < 0.05); Th1 cytokine expressions were decreased (P < 0.05), and Th2 cytokine levels were increased (P < 0.05). 3, 4-DAA also induced CD4(+) CD25(+) T cells expression (5.88 ± 2.1 vs 11.03 ± 2.93, P < 0.05) in mice MLNs. Transfer of these cells into TNBS colitis mice resulted in the reduction of the disease activity index (DAI) and histological scores. In LPMCs isolated from human Crohn's disease, 3, 4-DAA had the same effect. It can inhibit the cell proliferation, decrease Th1 cytokine expressions (P < 0.05), and increase Th2 cytokine levels (P < 0.05). The percentage of CD4(+) CD25(+) T cells were also increased (1.60 ± 0.14 vs 2.45 ± 0.50, P < 0.05). 1-MT treatment led to opposite outcomes.

Conclusion: 3, 4-DAA can alleviate the severity of colitis through inhibiting Th1 cells response, promoting Th2 cytokines expression and inducing CD4(+) CD25(+) T cells expression.

3-dioxygenase (IDO); 4-DAA); 4′-dimethoxycinnamonyl) anthranilic acid (3; Crohn's disease; N-(3′; TNBS colitis; indoleamine 2.