title: N-(3', 4'-dimethoxycinnamonyl) anthranilic acid alleviated experimental colitis by inhibiting autoimmune response and inducing CD4+ CD25+ regulatory T cells production.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wen
authors.forename: Liping
authors.initials: L
authors.lastname: Zhou
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D062367:ortho-Aminobenzoates / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; C587351:N-(3',4'-dimethoxycinnamonyl)anthranilic acid; D062367:ortho-Aminobenzoates; D014302:Trinitrobenzenesulfonic Acid
keywords: 3-dioxygenase (IDO); 4-DAA); 4′-dimethoxycinnamonyl) anthranilic acid (3; Crohn's disease; N-(3′; TNBS colitis; indoleamine 2