Academic Journal of Second Military Medical University (第二军医大学学报) 2008/28:9 PP.1069-1073
Objective:To study the influence of glucosidorum tripterygii tororum (GTT) and Mesalazine on the expression of IL-23, IL-17 and IL-12 in the colonic tissues of mice with rinitrobenzene sulphonic acid (TNBS)-induced acute colitis, and to study the possible mechanism.Methods: The C57BL/6 mice were divided into 4 groups, namely, a control group, a model group, a Mesalazine group and a GTT group. Colitis was induced by TNBS in the last 3 groups. The mice in the model group received no additional treatment; those in the GTT group received GTT daily by oral gavage 4 days before exposure to TNBS till the end of the experiment, and those in the Mesalazine group received Mesalazine enema solution daily 4 days before exposure till the end of the experiment. All the mice were sacrificed at 48 h after enema with TNBS. The macroscopic and histological scores of colon damage and myeloperoxidase (MPO) activity in colonic tissue were evaluated in every group. IL-23p19 and IL-17 contents in colonic tissues were measured by ELISA; the expression of IL-23p19, IL-17 and IL-12p35 mRNA in colonic tissues were examined by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-FQ-PCR) with SYBR Green Ⅰ.Results: Compared with the model group, GTT group and Mesalazine group had significantly lower macroscopic and histological scores and MPO activity (P<0.05). Expression of IL-23p19, IL-17 and IL-12p35 mRNA in the colonic tissues of the model group was significantly higher than that of the other 3 groups(P<0.05); the expression of IL-23p19, IL-17 protein was significant higher in the model group than that in the other 3 groups (P<0.05), with no significant difference found between the later 3 groups.Conclusion: GTT, like Mesalazine, can effectively inhibit inflammation in mice with TNBS-induced acute colitis through non-selectively inhibiting the expression of IL-23p19, IL-17 and IL-12p35.
 Iwakura Y,Ishigame H.The IL-23/IL-17 axis in inflammation[J].J Clin Invest,2006,116:1218-1222.
 McGovern D,Powrie F.The IL23 axis plays a key role in the pathogenesis of IBD[J].Gut,2007,56:1333-1336.
 Zhang Z,Zheng M,Bindas J,Schwarzenberger P,Kolls J K.Critical role of IL-17 receptor signaling in acute TNBS-induced colitis[J].Inflamm Bowel Dis,2006,12:382-388.
 Fujino S,Andoh A,Bamba S,Ogawa A,Hata K,Araki Y,et al.Increased expression of interleukin 17 in inflammatory bowel disease[J].Gut,2003,52:65-70.
 Schmidt C,Giese T,Ludwig B,Mueller-Molaian I,Marth T,Zeuzem S,et al.Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis[J].Inflamm Bowel Dis,2005,11:16-23.
 Mannon P J,Fuss I J,Mayer L,Elson C O,Sandborn W J,Present D,et al.Anti-interleukin-12 antibody for active Crohn's disease[J].N Engl J Med,2004,351:2069-2079.
 Bowman E P,Chackerian A A,Cua D J.Rationale and safety of anti-interleukin-23 and anti-interleukin-17A therapy[J].Curr Opin Infect Dis,2006,19:245-252.
 林琳,姜济民,戴惠珍.介绍我国独创的新抗炎药物——雷公藤多甙片[J].江苏医药,1985,3: 39-40.
 Butzner J D,Parmar R,Bell C J,Dalal V.Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat[J].Gut,1996,38:568-573.
 Dieleman L A,Palmen M J,Akol H,Bloemena E,Pena A S,Meuwissen S G,et al.Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines[J].Clin Exp Immunol,1998,114:385-391.
 Ye P,Rodriguez F H,Kanaly S,Stocking K L,Schurr J,Schwarzenberger P,et al.Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression,neutrophil recruitment,and host defense[J].J Exp Med,2001,194:519-527.
 Livak K J,Schmittgen T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J].Methods,2001,25:402-408.
 Calvo R,West J,Franklin W,Erickson P,Bemis L,Li E,et al.Altered HOX and WNT7A expression in human lung cancer[J].Proc Natl Acad Sci USA,2000,97:12776-12781.
 Smits H H,van Beelen A J,Hessle C,Westland R,de Jong E,Soeteman E,et al.Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development[J].Eur J Immunol,2004,34:1371-1380.
 Oppmann B,Lesley R,Blom B,Timans J C,Xu Y,Hunte B,et al.Novel p19 protein engages IL-12p40 to form a cytokine,IL-23,with biological activities similar as well as distinct from IL-12[J].Immunity,2000,13:715-725.
 Aggarwal S,Ghilardi N,Xie M H,de Sauvage F J,Gurney A L.Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17[J].J Biol Chem,2003,278:1910-1914.
 Awane M,Andres P G,Li D J,Reinecker H C.NF-kappa B-inducing kinase is a common mediator of IL-17-,TNF-alpha-,and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells[J].J Immunol,1999,162:5337-5344.