Modulation of epithelial cell response by P. gingivalis

牙龈卟啉单胞菌对上皮细胞反应的调节

• 批准号: 7183602
• 负责人: OZLEM YILMAZ
• 金额: $ 27.41万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183602
• 关键词: 1-Phosphatidylinositol 3-Kinase; Actins; Address; Adult; Affect; Anaerobic Bacteria; Antibiotics; Apoptosis; Apoptotic; Bacteria; Biochemical; Biological Assay; Camptothecin; Cardiovascular Diseases; Caspase; Cell Death; Cell Death Signaling Process; Cell Membrane Permeability; Cell Surface Receptors; Cell Survival; Cells; Cessation of life; Chemicals; Chronic; Cytoskeleton; DNA Fragmentation; Diabetes Mellitus; Disease; Down-Regulation; Elevation; Epithelial; Epithelial Cells; Epithelium; Equilibrium; Event; Family; Flow Cytometry; Fluorescence Microscopy; Focal Adhesion Kinase 1; Gingiva; Goals; Health; Healthcare Systems; Host Defense; IL8 gene; Immunoblotting; Induction of Apoptosis; Infection; Inhibition of Apoptosis; Injury; Integrins; Invaded; Investigation; Link; Mediating; Mediator of activation protein; Membrane; Microarray Analysis; Mitochondria; Molecular; NF-kappa B; Necrosis; Numbers; Outcome; Pathway interactions; Periodontal Diseases; Periodontitis; Phosphatidylserines; Phosphorylation; Phosphotransferases; Play; Population; Porphyromonas gingivalis; Premature Birth; Process; Property; RNA Interference; Regulation; Research Personnel; Research Proposals; Resistance; Risk Factors; Role; Signal Pathway; Signal Transduction; Site; Staurosporine; Stroke; Surface; Time; Tissues; Toll-like receptors; Western Blotting; base; caspase-9; cytochrome c; inhibitor/antagonist; microbial; microorganism; oral bacteria; oral infection; oral tissue; pathogen; paxillin; programs; receptor; response; selective expression

DESCRIPTION (provided by applicant): 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. Nevertheless, 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, and 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 U.S. 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.

描述（由申请人提供）：牙龈卟啉单胞菌是一种革兰氏阴性厌氧菌，被鉴定为与严重慢性牙周病相关的推定口腔细菌之一，是口腔组织的成功定植者，可以侵入原代牙龈上皮细胞（GEC）并在较长时间内保持活力。牙龈卟啉单胞菌能够在细胞内复制并调节GEC的许多表型和信号传导特性。与许多对其宿主有害的细胞内病原体不同，牙龈卟啉单胞菌不会诱导GEC的凋亡或坏死性死亡。此外，牙龈卟啉单胞菌感染保护GECs免受有效促凋亡剂诱导的凋亡。然而，牙龈卟啉单胞菌诱导的GECs细胞死亡信号通路和关键上游介质沿着生物化学和形态学改变的抑制机制尚未被表征。此外，微生物长期侵入GECs的后果与其在上皮内繁殖和传播感染的能力增加有关，以及感染细胞的命运仍有待确定。本项目的总体目标是描述牙龈卟啉单胞菌感染对宿主细胞状态的长期结果。具体而言，将通过检查整个感染过程中的细胞死亡-存活标志物和表型事件来研究感染细胞的最终命运。将表征由牙龈卟啉单胞菌介导的凋亡细胞应答的调节的潜在机制，并将确定微生物随时间在上皮内增殖和扩散的能力及其与宿主细胞存活的关系。将采用流式细胞术、荧光显微术、磷酸特异性蛋白质印迹活化测定、RNA干扰和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口的最普遍的多微生物疾病之一，并对卫生保健系统造成重大负担。此外，与牙龈卟啉单胞菌相关的口腔感染已被视为与心血管疾病、糖尿病、中风和早产等主要系统性健康问题有关的潜在风险因素。研究提出的目标将有助于牙龈卟啉单胞菌与宿主细胞相互作用的概念框架，并定义更有针对性的方法来控制牙龈卟啉单胞菌相关疾病。