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Clarification of the mechanism of periodontitis-initiated/accelerated atheroacleicsis and identification of its causal components

澄清牙周炎引发/加速动脉粥样硬化的机制并确定其病因成分

基本信息

批准号：
18592263
负责人：
YUMOTO Hiromichi
金额：
$ 2.47万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Emerging basic scientific studies have supported that infection may represent a risk factor for atherosclerosis. With periodotopathogenic bacteria, Porphyromonas gingivalis, as model pathogen, in vivo studies demonstrated that this organism can accelerate atheroma deposition in animal models. In this study, we first try to determine whether P. gingivalis can up-regulate the expression of the receptors for oxidized LDL in macrophage in vitro. We demonstrated that mouse macrophage cell line, J774.A1 cells were induced to express the receptors (SR-A, CD36 and Lox-1) for oxidized LDL by the stimulation with P. gingivalis, heat-killed bacteria or its fimbriae mutants. Moreover, we found that heat shock protein (HSP) 60 was also induced by the stimulation with P. gingivalis at both mRNA and protein levels. These data support that P. gingivalis stimulate macrophage differentiation to foam cells, a necessary initial event in the development of atherosclerotic plaque lesions.In this study, we i … More nvestigated the mechanisms of pro-inflammatory cytokine inductions in human monocytic cell line (THP-1 cells) by stimulation with recombinant histone-like DNA binding protein (HLP) of Streptococcus intermedius (rSi-HLP): rSi-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1β and TNF-α) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the cytokine induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK).Collectively, these results demonstrate oral, especially periodotopathic, bacteria can up-regulate inflammatory response and indicate the infection with these bacteria accelerates inflammatory responses, which directly lead to atherosclerosis. Less

新出现的基础科学研究支持感染可能是动脉粥样硬化的危险因素。以牙龈卟啉单胞菌为模型病原体，体内研究表明，该菌可加速动物模型中动脉粥样硬化的沉积。在本研究中，我们首先试图确定牙龈假单胞菌是否能在体外上调巨噬细胞氧化型低密度脂蛋白受体的表达。我们发现，小鼠巨噬细胞系J774.A1细胞在牙龈假单胞菌、热灭活菌或其菌毛突变体的刺激下，可表达氧化低密度脂蛋白受体(SR-A、CD36和Lox-1)。此外，我们还发现热休克蛋白(HSP)60也被牙龈假单胞菌刺激在mRNA和蛋白水平上被诱导。这些数据支持牙龈假单胞菌刺激巨噬细胞分化为泡沫细胞，这是动脉粥样硬化斑块病变发展过程中必要的初始事件。在本研究中，我们I…进一步探讨了重组中间链球菌组蛋白样DNA结合蛋白刺激人单核细胞系(THP-1细胞)产生促炎细胞因子的机制：重组中间链球菌组蛋白样DNA结合蛋白诱导的促炎细胞因子(IL-8、IL-1β和肿瘤坏死因子-α)的产生呈时间和剂量依赖性。与DNA结合的热稳定活性相比，RSI-HLP的细胞因子诱导活性是热不稳定的。在随后的研究中，RSI-HLP与脂磷壁酸、合成的Toll样受体2激动剂Pam3CSK4和胞内核苷酸结合的寡聚化结构域2受体激动剂室壁二肽协同作用。此外，Western印迹和特异性抑制剂阻断分析表明，RSI-HLP刺激诱导了细胞信号转导通路、细胞外信号调节激酶1/2(ERK1/2)和c-Jun氨基末端激酶(JNK)的激活。综上所述，这些结果表明口腔细菌，特别是骨膜病变细菌可以上调炎症反应，表明感染这些细菌加速了炎症反应，从而直接导致动脉粥样硬化。较少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

the Quintessence

精髓

DOI：
发表时间：
2015
期刊：
影响因子：
0
作者：
神尾宜昌;今井健一;田村宗明;Marni Cueno;清水一史;落合邦康;遠藤眞美;石田智洋;遠藤眞美，朝田和夫，呉明憲,朝田真理，竹川ひとみ，柿木保明，野本たかと;高柳篤史，遠藤眞美，長谷川功，木村益巳，野本たかと;石田智洋
通讯作者：
石田智洋

Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.

DOI：
10.1371/journal.ppat.0020076
发表时间：
2006-07
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Mydel P;Takahashi Y;Yumoto H;Sztukowska M;Kubica M;Gibson FC 3rd;Kurtz DM Jr;Travis J;Collins LV;Nguyen KA;Genco CA;Potempa J
通讯作者：
Potempa J

Proinflammatory roles of NOD2 in human gingival fibroblasts

NOD2 在人牙龈成纤维细胞中的促炎作用