Modulation of epithelial cell response by P. gingivalis

牙龈假单胞菌是一种革兰氏阴性厌氧菌，被认为是与严重、 慢性牙周病，是口腔组织的成功殖民者，并可侵袭和保留 在原代牙龈上皮细胞(GECs)中可存活较长时间。牙龈假单胞菌能够在细胞内 复制并调节GEC的许多表型和信号特性。与许多细胞内不同 牙龈假单胞菌是一种对宿主有害的病原体，它不会引起GEC的凋亡或坏死性死亡。 此外，牙龈假单胞菌感染可保护GECs免受强大的促凋亡剂诱导的细胞凋亡。 然而，抑制肾小管上皮细胞死亡信号通路的机制(S)及其关键上游 牙龈假单胞菌引起的介体及生化和形态改变尚未得到证实 特色化的。此外，微生物对GEC的长期入侵的后果 关于它日益增长的在上皮内繁殖和传播感染的能力以及命运 感染细胞的数量仍有待确定。 这个项目的总体目标是描绘牙龈假单胞菌感染对宿主细胞状态的长期结果。 具体地说，感染细胞的最终命运将通过检查细胞死亡-生存标记和 在整个感染过程中发生了表型事件。细胞凋亡调控的基本机制(S) 将对牙龈假单胞菌介导的反应进行表征，并研究微生物繁殖和 随着时间的推移，它在上皮内的扩散及其与宿主细胞生存的关系将被确定。流式细胞术， 荧光显微镜、磷酸特异的蛋白质印迹-激活分析、RNA干扰和 将采用基于微阵列的方法来实现这些目标。 牙周病是影响大多数美国人的最常见的多菌疾病之一 这对人口造成了巨大的负担，给卫生保健系统带来了沉重的负担。此外，口腔感染与 与牙龈假单胞菌有关的主要系统性健康问题的潜在危险因素，如 心血管疾病、糖尿病、中风和早产。对拟议目标的调查将 对牙龈假单胞菌与宿主细胞相互作用的概念框架作出贡献，并定义更多 控制牙龈假单胞菌相关疾病的针对性方法。

P. gingivalis, a gram negative anaerobe identified as one of the putative oral bacteria associated with severe, chronic forms of periodontal disease, is a successful colonizer of oral tissues, and can invade and remain viable for extended periods in primary gingival epithelial cells (GECs). P. gingivalis is capable of intracellular replication and modulates many phenotypic and signaling properties of GECs. Unlike many intracellular pathogens that are harmful to their host, P. gingivalis does not induce apoptotic or necrotic death in GECs. Furthermore, P. gingivalis infection protects GECs against apoptosis induced by potent pro-apoptotic agents. However, the mechanisms of inhibition of GECs cell death-signaling pathway(s) and the key upstream mediators along with biochemical and morphological alterations induced by P. gingivalis have not been characterized. In addition, the consequences of prolonged invasion of GECs by the microorganism with respect to its increasing ability to multiply and disseminate the infection within epithelium, as well as the fate of infected cells remain to be determined. Overall goal of this project is to delineate the long-term outcomes of P. gingivalis infection on host cell status. Specifically, ultimate fate of infected cells will be investigated by examining cell death-survival markers and phenotypic events throughout the infection. Underlying mechanism(s) of the modulation of apoptotic cell responses mediated by P. gingivalis will be characterized and the microorganism's ability to multiply and spread within epithelium over time and its relation to host cell survival will be determined. Flow cytometry, fluorescence microscopy, phospho-specific Western blotting-activation assays, RNA interference, and microarray based approaches will be employed to achieve these goals. Periodontal diseases are among the most prevalent polymicrobial diseases affecting a majority of US population and impose a significant burden on the health care system. Moreover, oral infections associated with P. gingivalis have been linked as potential risk factors to major systemic health problems such as cardiovascular disease, diabetes mellitus, stroke and premature births. Investigations of proposed aims will contribute to the conceptual framework of the P. gingivalis interaction with host cells and define more targeted approaches to control P. gingivalis associated diseases.