Epithelial Cell Sensing and Responses to P. gingivalis

描述：（由申请人提供）牙龈卟啉单胞菌，一种革兰氏（-）厌氧菌，具有 已被广泛认为是成人的主要病原体 牙周炎牙龈卟啉单胞菌成功地在硬组织和软组织中定植 口腔（牙齿和粘膜），并可以侵入和复制在人类牙龈 上皮细胞菌毛是介导粘附的主要决定因素。 牙龈也参与侵入过程。总体目标 本研究的主要目的是鉴定牙龈上皮细胞 牙龈卟啉单胞菌菌毛的上皮受体，以及 牙龈卟啉单胞菌菌毛受体诱导的细胞下游信号传导事件 约束力我们的初步工作已经确定整合素作为潜在的上皮细胞 牙龈卟啉单胞菌菌毛的细胞受体。整合素作为同源物的作用 牙龈卟啉单胞菌菌毛的受体和随后的信号转导 事件将是该提案的主要主题。菌毛-受体相互作用 将通过抗体和肽抑制试验，电子 显微镜和反义RNA技术。下游发生的事件 菌毛-受体结合将通过研究潜在的相互作用来检查 细胞信号和结构蛋白。酪氨酸磷酸化和反式- 这些蛋白质的共定位将被研究， 免疫沉淀、荧光显微镜和显微注射技术。我们 我希望这项研究能为理解 牙周病的发病机制，也有助于推进目前的 旨在预防或延缓疾病进程的治疗方案。

DESCRIPTION: (provided by applicant) P. gingivalis, a gram (-) anaerobe, has been recognized widely as the predominant pathogenic organism in adult periodontitis. P. gingivalis successfully colonizes the hard and soft tissues of the mouth (teeth and mucosa) and can invade and replicate in human gingival epithelial cells. Fimbriae are a major adherence-mediating determinant of P. gingivalis and also participate in the invasion process. The overall objectives of this study are the identification of the gingival epithelial cell receptor(s) for P. gingivalis fimbriae, and the determination of the epithelial cell downstream signaling events induced by P. gingivalis fimbriae-receptor binding. Our preliminary work has identified integrins as potential epithelial cell receptors for P. gingivalis fimbriae. The role of integrins as the cognate receptor for P. gingivalis fmbriae and in the subsequent signal transduction events will be main subject of this proposal. Fimbriae-receptor interactions will be investigated by antibody and peptide inhibition assays, electron microscopy and anti-sense RNA technology. The events that occur downstream of fimbriae-receptor binding will be examined by studying potentially interacting cell signaling and structural proteins. The tyrosine phosphorylation and trans- and colocalization of these proteins will be investigated by immunoprecipitation, fluorescence microscopy, and microinjection techniques. We expect this study will provide novel and crucial insights into understanding of the pathogenesis of periodontal diseases and also help advance the current treatment regimes designed to prevent or delay the disease process.