Attenuation of mycotoxin-induced IgA nephropathy by eicosapentaenoic acid in the mouse: dose response and relation to IL-6 expression.
Attenuation of mycotoxin-induced IgA nephropathy by eicosapentaenoic acid in the mouse: dose response and relation to IL-6 expression.
复制标题
DOI：
10.1016/j.jnutbio.2005.12.002
复制
发表时间：
2006-10
期刊：
影响因子：
--
通讯作者：
Yuhui Shi;J. Pestka
中科院分区：
文献类型：
--
作者：
Yuhui Shi;J. Pestka
临床试验表明，膳食 (n-3) 多不饱和脂肪酸 (PUFA) 补充剂可抑制免疫球蛋白 A 肾病 (IgAN)（人类肾小球肾炎最常见的形式）的进展。 IgAN 的早期阶段可以通过给小鼠喂食霉菌毒素脱氧雪腐镰刀菌烯醇 (DON) 来模拟。在此，评估了消耗 (n-3) PUFA 二十碳五烯酸 (EPA) 对 DON 诱导的 IgAN 的影响，涉及剂量依赖性和白细胞介素 (IL-6) 的表达。在剂量反应研究中，食用 20 ppm DON 并补充 0%、0.1%、0.5% 和 3% EPA 16 周的小鼠，体重增加和采食量没有差异。饲喂两种最高 EPA 浓度的小鼠表现出脾脏 EPA、二十二碳五烯酸和二十二碳六烯酸显着增加，而在所有三个 EPA 饲喂组中，花生四烯酸均减少。脱氧雪腐镰刀菌烯醇的消耗显着增加血清 IgA 和 IgA 免疫复合物以及肾系膜 IgA 沉积。在喂食 3% EPA 饮食的小鼠中，所有三种 IgAN 标记物均减弱，但在喂食 0.1% 或 0.5% EPA 的小鼠中则没有。在对照饮食中饲喂 DON 的小鼠的脾脏和派尔氏集结 (PP) 细胞培养物中观察到 IgA 产量升高，但在饲喂 0.1%、0.5% 和 3% EPA 的小鼠的培养物中，IgA 产量减少。急性 DON 暴露会增加血清 IL-6 水平，IL-6 是一种细胞因子，可驱动 IgA 定向 B 细胞分化为 IgA 分泌。相关地，脾脏和 PP 中 IL-6 mRNA 和 IL-6 异核 RNA（IL-6 转录标志物）的表达增加。在消耗 3% EPA 的小鼠中，IL-6 表达的所有三个指标均受到抑制。 IL-6 的抑制对应于调节该细胞因子转录的两个因子（环 AMP 反应元件结合蛋白和激活蛋白 1）的结合活性降低。结果表明，EPA 相对于实验性 IgAN 的抑制存在阈值，并且该阈值剂量可有效抑制 IL-6 转录。
Clinical trials have revealed that progression of immunoglobulin A nephropathy (IgAN), the most common form of human glomerulonephritis, is inhibited by dietary (n-3) polyunsaturated fatty acid (PUFA) supplementation. The early stages of IgAN can be mimicked by feeding mice the mycotoxin deoxynivalenol (DON). Here, the effects of consuming the (n-3) PUFA eicosapentaenoic acid (EPA) on DON-induced IgAN were assessed relative to dose dependency and to expression of interleukin (IL-6). In the dose-response study, weight gain and feed intake did not differ among mice consuming 20 ppm DON supplemented with 0%, 0.1%, 0.5% and 3% EPA for 16 weeks. Mice fed the two highest EPA concentrations exhibited markedly increased splenic EPA, docosapentaenoic acid and docosahexaenoic acid, whereas arachidonic acid was decreased in all three EPA fed groups. Deoxynivalenol consumption significantly increased serum IgA and IgA immune complexes as well as kidney mesangial IgA deposition. All three IgAN markers were attenuated in mice fed 3% EPA diet but not in those fed 0.1% or 0.5% EPA. Elevated IgA production was observed in spleen and Peyer's patch (PP) cell cultures derived from mice fed DON in control diets, but this was reduced in cultures from mice fed 0.1%, 0.5% and 3% EPA. Acute DON exposure increased serum levels of IL-6, a cytokine that drives differentiation of IgA-committed B cells to IgA secretion. Relatedly, expression of IL-6 mRNA and IL-6 heteronuclear RNA, a marker of IL-6 transcription, was increased in spleen and PP. All three indicators of IL-6 expression were suppressed in mice consuming 3% EPA. Suppressed IL-6 corresponded to decreased binding activity of two factors that regulate transcription of this cytokine, cyclic AMP response element-binding protein and activator protein-1. The results indicate that a threshold existed for EPA relative to suppression of experimental IgAN and that the threshold dose was effective at inhibiting IL-6 transcription.