Genomics Periodontal Host-Parasite Interactions

基因组学牙周宿主-寄生虫相互作用

• 批准号: 6855755
• 负责人: Salomon Amar
• 金额: $ 40.38万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6855755
• 关键词: Bacteroides gingivalis; bacteria infection mechanism; biological signal transduction; host organism interaction; interleukin 1; interleukin 6; interleukin 8; laboratory mouse; lipopolysaccharides; microarray technology; monocyte; northern blottings; oral bacteria; oral health; periodontitis; pilus; polymerase chain reaction; proteomics; tumor necrosis factor alpha; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): Periodontitis is an inflammatory disease with host-parasite interactions known to contribute to connective tissue destruction and alveolar bone resorption the landmark of this disease. Porphyromonas gingivalis (P.g.), a black-pigmented Gram-negative anaerobic bacterium, has been implicated as a major periodontal pathogen in the development and progression of periodontal disease. Structures on its bacterial cell wall and appendage, such as lipopolysaccharide (LPS) and fimbriae, play important roles in the induction of innate immune responses, including cytokine production by localized and circulating leukocytes, such as monocyte/macrophage. Based on our preliminary data, we hypothesize that live P.g. stimulates unique pro-inflammatory signal transduction pathways in human PBM as opposed to purified bacterial components, such as P.g. LPS or P.g. fimbriac. To test this, the following specific aims are proposed: Aim 1: To test at the transcriptional level the hypothesis that unique signaling pathways are differentially induced by live P.g., P.g. LPS and P.g. fimbriae in human peripheral blood monocytes. Aim 2: To test at the level of protein expression the hypothesis that unique signaling pathways are differentially induced by live P.g., P.g. LPS and P.g. fimbriac in human PBM. Aim 3: To establish the functional significance of unique signaling pathways identified in Aims 1 and 2 we will test them in vitro and in vivo. The results of these studies should provide a new gateway to our understanding of the etiology and pathogenesis of periodontal diseases. Since the differential host innate response identified in our preliminary data may in fact represent different stages of the periodontal infection, the results are expected to have important therapeutic implications.

描述(申请人提供)：牙周炎是一种炎症性疾病，宿主和寄生虫的相互作用导致结缔组织破坏和牙槽骨吸收，是这种疾病的标志。牙龈卟啉单胞菌是一种黑色革兰氏阴性厌氧菌，已被认为是牙周疾病发生发展的主要致病菌。细菌细胞壁和附属物上的结构，如脂多糖(LPS)和菌毛，在诱导先天性免疫反应中发挥重要作用，包括局部和循环中的白细胞，如单核/巨噬细胞产生细胞因子。根据我们的初步数据，我们假设直播的P.G.刺激人PBM中独特的促炎信号转导通路，而不是纯化的细菌成分，如P.G.LP或P.G.海马伞。为了验证这一点，提出了以下具体目标：目标1：在转录水平上验证独特的信号通路是由活体P.G.、P.G.LP和P.G.人外周血单核细胞中的菌毛。目的2：在蛋白表达水平上验证活体P.G.、P.G.LP和P.G.人外周血中的菌毛。目的：为了确定AIMS 1和AIMS 2中识别的独特信号通路的功能意义，我们将在体外和体内对它们进行测试。这些研究的结果应该为我们理解牙周病的病因和发病机制提供一个新的途径。由于在我们的初步数据中发现的宿主先天反应的差异实际上可能代表牙周感染的不同阶段，因此该结果有望具有重要的治疗意义。