Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation.
Select phytochemicals suppress human T-lymphocytes and mouse splenocytes suggesting their use in autoimmunity and transplantation.
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DOI：
10.1016/j.nutres.2009.08.003
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Crawford DR
中科院分区：
文献类型：
--
作者：
Hushmendy S;Jayakumar L;Hahn AB;Bhoiwala D;Bhoiwala DL;Crawford DR
我们已经考虑了一种新的“合理的”基因靶向治疗的方法，其遗传基础是使用选择的植物化学物质定义的病理。我们推断，这种方法的一个潜在应用是需要免疫抑制的疾病，如自身免疫性疾病和移植，其中遗传靶点被明确定义;即，白细胞介素-2和相关的T细胞活化。因此，我们假设，选择植物化学物质可以抑制T淋巴细胞增殖在体外和体内。检测了浆果提取物、姜黄素、槲皮素、萝卜硫素、表没食子儿茶素没食子酸酯（EGCG）、白藜芦醇、α-生育酚、维生素C和蔗糖对培养的抗CD 3+抗CD 28激活的原代人T淋巴细胞的免疫抑制作用。姜黄素、萝卜硫素、槲皮素、浆果提取物和表没食子儿茶素没食子酸酯均显著抑制T细胞增殖，并且这种作用不是由于毒性。这些药物还减少了IL-2的产生，表明这种重要的T细胞细胞因子参与了增殖抑制。除浆果提取物外，这些相同的药物也抑制小鼠脾T细胞增殖和IL-2的产生。随后的体内研究表明，槲皮素（但不是萝卜硫素）适度抑制小鼠脾细胞增殖后补充BALB/c小鼠的饮食。如果校正如在培养的T细胞中观察到的补充剂“回忆”的损失，则这种效果尤其突出。这些结果表明，这些选择的植物化学物质用于治疗自身免疫和移植患者的潜在用途，并支持我们使用选择的植物化学物质治疗遗传定义的病理学的策略，我们认为这种方法简单，健康，具有成本效益。
We have considered a novel “rational” gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, α-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement “recall” as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective.
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影响因子：
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