3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo
3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo
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DOI：
10.1016/j.jnutbio.2007.05.004
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发表时间：
2008-05-01
影响因子：
5.6
通讯作者：
Bjeldanes, Leonard F.
中科院分区：
文献类型：
--
作者：
Xue, Ling;Pestka, James J.;Bjeldanes, Leonard F.
3，3 '-二吲哚基甲烷（DIM）是吲哚-3-甲醇的主要缩合产物，在癌症动物模型中表现出化学预防特性。最近的研究表明，DIM刺激干扰素-γ（IFN-γ）的产生，并通过包括IFN-γ受体表达增加的机制增强人乳腺癌细胞中的IFN-γ信号传导途径。本研究的目的是检验DIM调节小鼠免疫功能的假设。具体而言，在一组鼠免疫功能测试中评估DIM的作用，所述测试包括脾细胞增殖、活性氧（ROS）产生、细胞因子产生和对病毒感染的抗性。发现DIM诱导脾细胞增殖，以及增加有丝分裂原和白细胞介素（IL）-2诱导的脾细胞增殖。DIM还刺激小鼠腹腔巨噬细胞培养物产生ROS。DIM经口给药（而非腹腔注射）诱导小鼠血清细胞因子升高，包括IL-6、粒细胞集落刺激因子（G-CSF）、IL-12和IFN-γ。最后，在肠道病毒感染模型中，小鼠口服DIM增强了G1道呼肠孤病毒的清除和随后的粘膜伊加反应。因此，DIM是免疫功能的有效刺激剂。这种性质可能有助于这种吲哚的癌症抑制作用。(c)2008年爱思唯尔公司All rights reserved.
3,3'-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol, exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-gamma) production and potentiates the IFN-gamma signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-gamma receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the effects of DIM were evaluated in a panel of murine immune function tests that included splenocyte proliferation, reactive oxygen species (ROS) generation, cytokine production and resistance to viral infection. DIM was found to induce proliferation of splenocytes as well as augment mitogen- and interleukin (IL)-2-induced splenocyte proliferation. DIM also stimulated the production of ROS by murine peritoneal macrophage cultures. Oral administration of DIM, but not intraperitoneal injection, induced elevation of serum cytokines in mice, including IL-6, granulocyte colony-stimulating factor (G-CSF), IL-12 and IFN-gamma. Finally, in a model of enteric virus infection, oral DIM administration to mice enhanced both clearance of reovirus from the G1 tract and the subsequent mucosal IgA response. Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole. (c) 2008 Elsevier Inc. All rights reserved.