Faculty of Life Sciences, Department of Nutritional Science, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Benef Microbes. 2012 Jun 1;3(2):91-8. doi: 10.3920/BM2011.0052.
Strain specific properties of probiotics in providing supportive health effects in the immune system and the gastrointestinal tract have been widely investigated in vivo and in vitro. However, the underlying responsible mechanism is poorly described. By unravelling the probiotic-induced responses in a complex network of interacting signalling pathways, we investigated the effect of heat-inactivated Lactobacillus rhamnosus GG (LGG) and Lactobacillus delbrueckii subsp. bulgaricus (L.del) on the expression of TLR4 and signalling factors such as p38 MAPK and I?B at transcription level in human monocyte-derived dendritic cells (DCs). Our findings demonstrated that even inactivated probiotic strains can affect TLR4 expression in a down-regulatory direction as with lipopolysaccharides after 12 hours. LGG significantly down-regulated expression of p38 while I?B expression was significantly reduced in L.del-treated DCs. Moreover, we found these Lactobacillus strains could even modify the immune response at post-transcriptional level by modifying miRNAs expression. Based on our results LGG induced a significant down-regulatory effect on miR-146a expression which is known as a novel fine negative regulator of immune response targeting NFκB. On the other hand, miR-155 was up-regulated by LGG which is consistent with down-regulation of p38 and in LGG-treated DCs. These findings provide genetic and epigenetic explanations for the responsible underlying mechanisms by which probiotics influence immune response by targeting DCs.
益生菌在免疫系统和胃肠道中提供支持健康效应的菌株特异性特性已在体内和体外得到广泛研究。然而，其潜在的负责机制描述得很差。通过揭示益生菌在相互作用的信号通路复杂网络中引起的反应，我们研究了热灭活鼠李糖乳杆菌 GG（LGG）和德氏乳杆菌保加利亚亚种（L.del）对人单核细胞衍生树突状细胞（DC）中 TLR4 和信号因子（如 p38 MAPK 和 I?B）表达的影响转录水平。我们的研究结果表明，即使是失活的益生菌株也可以像脂多糖一样在 12 小时后以负调控的方式影响 TLR4 的表达。LGG 显著下调 p38 的表达，而 L.del 处理的 DCs 中 I?B 的表达明显降低。此外，我们发现这些乳酸菌株甚至可以通过修饰 miRNA 的表达来修饰免疫反应。基于我们的结果，LGG 诱导 miR-146a 表达的显著下调，miR-146a 是一种针对 NFκB 的新型免疫反应负调控因子。另一方面，miR-155 被 LGG 上调，这与 p38 的下调以及 LGG 处理的 DCs 一致。这些发现为益生菌通过靶向 DCs 影响免疫反应的负责潜在机制提供了遗传和表观遗传解释。
