Regulation of intestinal immune networks by the DNA motifs from probiotics.

益生菌 DNA 基序对肠道免疫网络的调节。

• 批准号: 11660265
• 负责人: KITAZAWA Haruki
• 金额: $ 2.3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660265/
• 关键词: Probiotics; Cytokine; L.bulgaricus; mucosal immunity; DNA; IL-7; Cloning; Th1; IFNγ; IL-12; ブタ; Probiotics; Cytokine; L.bulgaricus; mucosal immunity; DNA; IL-7; Cloning; Th1; IFNγ; IL-12; ブタ

A great interest has increased concerning the therapeutic and preventive effects of yogurt against several diseases. Lactobacillus delbrueckii ssp. bulgaricus (L.bulgaricus) and Streptococcus thermophilus (S.thermophilus), which are dairy lactic acid bacteria (LAB), has been commonly used in yogurt production in the world. In our recent study, we have been particularly focusing on the DNA from yogurt starter cultures as one of the immunomoduratory factors in the LAB.The present study was conducted to elucidate the immunomoduratory functions of the DNA in the gut. The DNA from L.bulgaricus and S.thermophilus significantly stimulated mitogenic responses to murine peyer's patch cells and induced CD69 on the cells. The active DNA was cloned and the DNA motif, looks like CpG motif, was found in L.bulgaricus NIAI B6. L.bulgaricus NIAI B6 was passed through the M cells and digested by macrophage/dendritic cells result in the stimulation of immune cells by the DNA motif. The binding and ingestion of the DNA motif were demonstrated in peyer's patch cells. The DNA motif augmented induction of Th1 type cytokine (IL-7, IL-12, IL-18, IFNγ) mRNA in peyer's patches. Since swine will be valuable as a human model, swine IL-7 cDNA was isolated from neonatal intestinal epithelium by the RACE methods with designated primers based on the conserved sequences of the other mammalian IL-7. Cytokine producing cells induced by the DNA motif were detected in several immune cells such as B, NK, NKT and Dendritic cells. This study demonstrated that mucosal immunostimulatory DNA motif exist in L.bulgaricus NIAI B6 and proposed that the microorganism is a good candidate of a starter culture for the production of new functional foods, "Bio-Defense Foods".

人们对酸奶对多种疾病的治疗和预防作用的极大兴趣增加了。乳杆菌Delbrueckii SSP。保加利亚（L. bulgaricus）和嗜热链球菌（S. thermophilus），它们是乳乳酸菌（LAB），通常用于世界上酸奶的生产中。在我们最近的研究中，我们特别关注酸奶起动培养物的DNA，作为实验室中的免疫调节因子之一。进行了本研究以阐明肠道中DNA的免疫调节功能。来自乳腺乳杆菌和舒mophilus的DNA显着刺激了对鼠Peyer斑块细胞的有丝分裂反应，并在细胞上诱导了CD69。将活性DNA克隆，并在L.Bulgaricus niAi B6中发现DNA基序，看起来像CpG基序，并通过M细胞，并被巨噬细胞/树突状细胞消化，从而导致DNA基序刺激免疫细胞。在Peyer的斑块细胞中证明了DNA基序的结合和摄入。 DNA基序增强了PEYER斑块中Th1型细胞因子（IL-7，IL-12，IL-18，IFNγ）mRNA的诱导。由于猪作为人类模型的有价值，因此通过种族方法从新生儿肠上皮分离猪IL-7 cDNA，并根据其他哺乳动物IL-7的配置序列指定的引物。在B，NK，NKT和树突状细胞等几个免疫细胞中检测到由DNA基序诱导的细胞因子生产细胞。这项研究表明，l.bulgaricus niAi B6存在粘膜免疫刺激性DNA基序，并提出微生物是生产新功能性食品的启动培养物的良好候选者，即“生物防御食品”。