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高可可摄入量下调大鼠肠道 IgA 的机制。

Mechanisms involved in down-regulation of intestinal IgA in rats by high cocoa intake.

机构信息

Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, E-08028 Barcelona, Spain.

出版信息

J Nutr Biochem. 2012 Jul;23(7):838-44. doi: 10.1016/j.jnutbio.2011.04.008. Epub 2011 Aug 12.

DOI:10.1016/j.jnutbio.2011.04.008
PMID:21840190
Abstract

Previous studies have shown that rat intestinal immunoglobulin A (IgA) concentration and lymphocyte composition of the intestinal immune system were influenced by a highly enriched cocoa diet. The aim of this study was to dissect the mechanisms by which a long-term high cocoa intake was capable of modifying gut secretory IgA in Wistar rats. After 7 weeks of nutritional intervention, Peyer's patches, mesenteric lymph nodes and the small intestine were excised for gene expression assessment of IgA, transforming growth factor β, C-C chemokine receptor-9 (CCR9), interleukin (IL)-6, CD40, retinoic acid receptors (RARα and RARβ), C-C chemokine ligand (CCL)-25 and CCL28 chemokines, polymeric immunoglobulin receptor and toll-like receptors (TLR) expression by real-time polymerase chain reaction. As in previous studies, secretory IgA concentration decreased in intestinal wash and fecal samples after cocoa intake. Results from the gene expression showed that cocoa intake reduced IgA and IL‑6 in Peyer's patches and mesenteric lymph nodes, whereas in small intestine, cocoa decreased IgA, CCR9, CCL28, RARα and RARβ. Moreover, cocoa-fed animals presented an altered TLR expression pattern in the three compartments studied. In conclusion, a high-cocoa diet down-regulated cytokines such as IL-6, which is required for the activation of B cells to become IgA-secreting cells, chemokines and chemokine receptors, such as CCL28 and CCR9 together with RARα and RARβ, which are involved in the gut homing of IgA-secreting cells. Moreover, cocoa modified the cross-talk between microbiota and intestinal cells as was detected by an altered TLR pattern. These overall effects in the intestine may explain the intestinal IgA down-regulatory effect after the consumption of a long-term cocoa-enriched diet.

摘要

先前的研究表明,高可可饮食会影响大鼠肠道免疫球蛋白 A(IgA)浓度和肠道免疫系统淋巴细胞组成。本研究旨在剖析长期高可可摄入能够改变 Wistar 大鼠肠道分泌型 IgA 的机制。经过 7 周的营养干预后,取出派尔集合淋巴结、肠系膜淋巴结和小肠,通过实时聚合酶链反应评估 IgA、转化生长因子 β、C-C 趋化因子受体 9(CCR9)、白细胞介素(IL)-6、CD40、视黄酸受体(RARα 和 RARβ)、C-C 趋化因子配体(CCL)-25 和 CCL28 趋化因子、多聚免疫球蛋白受体和 Toll 样受体(TLR)的基因表达。与之前的研究一样,摄入可可后,肠道冲洗液和粪便样本中的分泌型 IgA 浓度降低。基因表达结果表明,可可摄入降低了派尔集合淋巴结和肠系膜淋巴结中的 IgA 和 IL-6,而在小肠中,可可降低了 IgA、CCR9、CCL28、RARα 和 RARβ。此外,食用可可的动物在三个研究部位表现出改变的 TLR 表达模式。总之,高可可饮食下调了细胞因子(如 IL-6)的表达,IL-6 是激活 B 细胞成为分泌 IgA 的细胞所必需的,下调了趋化因子和趋化因子受体(如 CCL28 和 CCR9)以及参与 IgA 分泌细胞肠道归巢的 RARα 和 RARβ。此外,可可通过改变 TLR 模式改变了微生物群和肠道细胞之间的串扰。这些肠道的总体影响可能解释了长期摄入可可富集饮食后肠道 IgA 下调的原因。

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