Epithelial Cell Sensing and Responses to P. gingivalis

描述：(申请人提供)牙龈假单胞菌是一种革兰氏阴性厌氧菌，已被广泛认为是成人的主要致病微生物。 牙周炎。牙龈假单胞菌成功定植硬组织和软组织 位于口腔(牙齿和粘膜)，可侵入并复制到人类牙龈中 上皮细胞。菌毛是P。 也参与了牙周炎的侵袭过程。总体目标 这项研究的主要内容是牙龈上皮细胞的鉴定 牙龈假单胞菌菌毛受体(S)及其上皮细胞的测定 牙龈假单胞菌菌毛受体诱导的细胞下游信号事件 有约束力的。我们的初步工作已经确定整合素是潜在的上皮细胞 牙龈假单胞菌菌毛的细胞受体。整合素作为同源物的作用 牙龈假单胞菌菌毛受体及其后续的信号转导 事件将是这项提案的主要主题。菌毛-受体相互作用 将通过抗体和多肽抑制分析进行研究，电子 显微镜和反义RNA技术。发生在下游的事件 菌毛与受体的结合将通过研究潜在的相互作用来检验 细胞信号和结构蛋白。酪氨酸磷酸化和反式- 这些蛋白质的共存将通过以下方式进行研究 免疫沉淀、荧光显微镜和显微注射技术。我们 预计这项研究将为理解 对牙周病发病机制的研究也有助于推进当前 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.