Isoflavones regulate innate immunity and inhibit experimental colitis

Isoflavones regulate innate immunity and inhibit experimental colitis
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DOI:
10.1111/j.1440-1746.2008.05714.x
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发表时间:
2009-06-01
影响因子:
4.1
通讯作者:
Wakatsuki, Yoshio
Wakatsuki, Yoshio
中科院分区:
医学3区
文献类型:
--
作者:
Morimoto, Masakazu;Watanabe, Tomohiro;Wakatsuki, Yoshio

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肠道对腔内抗原的免疫反应失调可引起炎性肠病(IBD)。膳食抗原在IBD发病机制或预防中的作用尚不清楚。大豆异黄酮被大量消化,具有多种生物活性。本研究的目的是确定糖糖和生物可利用形式的异黄酮是否对结肠炎小鼠模型的肠道免疫和保护宿主免受组织损伤有任何影响。给小鼠灌胃富含大豆苷元异黄酮苷元(DRIA) 1周后,用2%葡聚糖硫酸钠(DSS)灌胃4天诱导结肠炎。通过检查结肠组织病理学、体重变化和肠系膜淋巴结细胞(MLN)的功能分析来评估DRIA的效果。DRIA以剂量依赖的方式抑制toll样受体(TLR)2和tlr4刺激的单核细胞产生白细胞介素(IL)-6和IL-8。与对照组小鼠相比,给予DRIA的小鼠结肠炎症和组织损伤更少。DRIA的这种保护作用与MLN中干扰素γ、IL-6和IL-12p40分泌减少,il -10分泌增加和抗原呈递细胞(APC)的低细胞活化状态有关。摄入DRIA可下调APC功能,抑制DSS结肠炎。
Dysregulated immune responses in the gut to luminal antigens can cause inflammatory bowel diseases (IBD). The roles played by dietary antigens in the pathogenesis or prevention of IBD are poorly understood. Soybean isoflavones are digested in large amounts and have many biological activities. The aim of this study was to determine whether isoflavones in aglycon and bioavailable forms have any effect on gut immunity and protect the host from tissue damage in a mouse model of colitis.We administered daidzein-rich isoflavone aglycones (DRIA) to mice for 1 week and then treated them with 2% dextran sodium sulfate (DSS) in drinking water for 4 days to induce colitis. The effect of DRIA was evaluated by examining the histopathology of the colon, body weight changes, and functional analysis of mesenteric lymph node cells (MLN).DRIA inhibited interleukin (IL)-6 and IL-8 production by Toll-like receptor (TLR)2, and TLR4-stimulated monocytes in a dose-dependent manner. The mice administered DRIA had less inflammation and tissue damage in the colon than the control mice. This protective effect of DRIA was associated with a decrease in interferon-gamma, IL-6, and IL-12p40 secretion, and an increase in IL-10secretion and low cell-activation status of antigen-presenting cells (APC) in MLN.Ingested DRIA can downregulate the functions of APC and inhibit DSS colitis.