Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.
Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.
复制标题
吗替麦考酚酯调节活动性克罗恩病小鼠模型中 Th1/Th2 的分化和细胞因子的分泌
DOI：
10.3390/ijms161125985
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发表时间：
2015-11-06
影响因子：
5.6
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Lv QK;Liu JX;Li SN;Gao YJ;Lv Y;Xu ZP;Huang BX;Xu SY;Yang DX;Zeng YL;Liu DF;Wang W
麦考酚酸酯（MMF）是一种替代免疫抑制剂，据报道对治疗难治性炎症性肠病（IBD）有效且耐受性良好。本研究旨在探讨霉酚酸酯（MMF）对克罗恩病（CD）引起的肠道损伤和组织炎症的治疗作用。在这里，三硝基苯磺酸（TNBS）结肠炎诱导小鼠，然后，我们测量了小鼠脾细胞中的Th 1/Th 2细胞的分化，通过流式细胞术和实时聚合酶链反应和/或酶联免疫吸附试验（RT-PCR/ELISA）的TNBS诱导的结肠炎小鼠细胞因子的分泌。结果显示，在TNBS诱导的结肠炎小鼠中，MMF显著抑制促炎细胞因子IFN-γ、TNF-α、IL-12、IL-6和IL-1β的mRNA表达;但MMF不抑制IL-10 mRNA的表达。此外，ELISA显示，在TNBS结肠炎模型中，IFN-γ、TNF-α、IL-12、IL-6和IL-1β的血清水平下调。流式细胞仪分析显示，霉酚酸酯显着降低CD小鼠模型中的Th 1和Th 2脾细胞的百分比。霉酚酸（MPA）也显著降低体外脾Th 1和Th 2细胞的百分比。此外，霉酚酸酯治疗不仅显着改善腹泻，体重减轻，但也消除了炎症性结肠炎的组织病理学严重程度和炎症反应，并增加TNBS诱导的结肠炎小鼠的存活率。这些结果表明，用霉酚酸酯治疗可以改善实验性结肠炎，并通过调节Th 1/Th 2细胞的分化下调促炎细胞因子诱导CD的炎症反应缓解。
Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn’s disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.