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益生菌混合物VSL#3在C57BL/6和BALB/c小鼠的骨髓来源树突状细胞中介导促炎和抗炎反应。

The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice.

作者信息

Mariman Rob, Kremer Bas, Koning Frits, Nagelkerken Lex

机构信息

Department of Metabolic Health Research,TNO,Zernikedreef 9, 2333 CK,Leiden,The Netherlands.

Department of Immunohematology and Blood Transfusion,Leiden University Medical Centre,Leiden,The Netherlands.

出版信息

Br J Nutr. 2014 Oct 14;112(7):1088-97. doi: 10.1017/S000711451400169X. Epub 2014 Sep 2.

Abstract

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain more insights into the underlying mechanisms, in the present study, we analysed the modulation of bone marrow-derived dendritic cells (BM-DC) from BALB/c (T helper (Th)2 biased) v. C57BL/6 (Th1 biased) mice. Our findings showed that VSL#3 differed from pure Toll-like receptor (TLR) ligands by inducing the production of various cytokines, including IL-12 p70 subunit (IL-12p70), IL-23 and IL-10. Dedicated TLR arrays were employed to profile mRNA from BM-DC cultured with lipopolysaccharide (LPS), VSL#3, or a combination of both. This approach led to the identification of (1) a cluster of genes that were up- or down-regulated, irrespective of the stimulus, (2) a cluster of genes that were synergistically up-regulated by LPS and VSL#3 in BM-DC from C57BL/6 mice, but not in those from BALB/c mice, and (3) a cluster of LPS-induced genes that were suppressed by VSL#3, in particular chemokine genes. These data show that this probiotic mixture has both pro- and anti-inflammatory effects on BM-DC and suggest that their immune-modulating properties in vivo may depend on the genetic background of the host.

摘要

益生菌可表达多种分子结构,这些结构可与固有免疫细胞上的受体结合,并介导宿主的健康促进作用。我们最近在一个结肠炎模型中证明,益生菌混合物VSL#3的有益作用可能部分归因于对肠道趋化因子表达的抑制。为了更深入了解其潜在机制,在本研究中,我们分析了来自BALB/c(偏向T辅助细胞(Th)2)与C57BL/6(偏向Th1)小鼠的骨髓来源树突状细胞(BM-DC)的调节情况。我们的研究结果表明,VSL#3与纯 Toll样受体(TLR)配体不同,它可诱导多种细胞因子的产生,包括IL-12 p70亚基(IL-12p70)、IL-23和IL-10。我们使用专用的TLR阵列分析用脂多糖(LPS)、VSL#3或两者组合培养的BM-DC的mRNA。这种方法导致鉴定出:(1)一组无论刺激如何都会上调或下调的基因;(2)一组在C57BL/6小鼠的BM-DC中被LPS和VSL#3协同上调,但在BALB/c小鼠的BM-DC中未出现这种情况的基因;(3)一组被VSL#3抑制的LPS诱导基因,特别是趋化因子基因。这些数据表明,这种益生菌混合物对BM-DC具有促炎和抗炎作用,并表明它们在体内的免疫调节特性可能取决于宿主的遗传背景。

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