Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide pattern
Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide pattern
复制标题
DOI：
10.1111/j.1462-5822.2004.00470.x
复制
发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Iliev, ID;Kitazawa, H;Saito, T
已知来自鼠李糖乳杆菌GG（LGG）的全细胞、细胞壁组分和一些可溶性因子在与动物和人免疫细胞相互作用时引起免疫应答。在本研究中，我们发现LGG的染色体DNA是小鼠脾B细胞增殖、CD 86/CD 69表达和细胞因子产生的有效诱导剂。在LGG的基因组DNA中，我们发现了TTTCGTTT寡脱氧核苷酸（ODN）ID 35，它在许多免疫刺激试验中具有有效的活性。ID 35的活性不需要硫代磷酸骨架。在B细胞增殖、CD 86/CD 69表达、白细胞介素（IL）-6、IL-12、IL-18、干扰素γ（IFN-γ）和肿瘤坏死因子α（TNF-α）mRNA表达以及IFN-γ/IL-12 p70蛋白产生测定中，ODN ID 35显示出与鼠原型ODN 1826诱导的活性水平相当的活性水平。此外，ID 35似乎在鼠和人免疫细胞中具有同等活性。这些刺激作用是由于位于ID 35的5'端的TTTCGTTT基序。在这项研究中，我们首次证明，从LGG的DNA是一个因素的免疫生物活性。此外，ODN ID 35是第一个在免疫生物素细菌DNA中发现的具有如此强的免疫刺激活性的ODN。
Whole cells, cell wall components and some soluble factors from Lactobacillus rhamnosus GG (LGG) are known to invoke immune responses as they interact with animal and human immune cells. In the present study, we found that chromosomal DNA from LGG is a potent inducer of splenic B cell proliferation, CD86/CD69 expression and cytokine production in mice. In the genomic DNA of LGG we discovered TTTCGTTT oligodeoxynucleotide (ODN) ID35, which has a potent activity in a number of immunostimulatory assays. Phosphorothioate backbone is not required for the activity of ID35. The ODN ID35 showed levels of activity comparable with those induced by the murine prototype ODN 1826 in B cell proliferation, CD86/CD69 expression, interleukin (IL)-6, IL-12, IL-18, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) mRNA expression and IFN-gamma/IL-12p70 protein production assays. Additionally, ID35 appeared to be equally active in both murine and human immune cells. These stimulatory effects are due to TTTCGTTT motif located in the 5' end of ID35. In this study we demonstrate for a first time that, DNA from LGG is a factor of immunobiotic activity. Furthermore, ODN ID35 is the first ODN, with such a strong immunostimulatory activity to be found in immunobiotic bacterial DNA.