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: 7932534
• 负责人: OZLEM YILMAZ
• 金额: $ 8.46万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932534
• 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; 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; 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

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.

牙龈卟啉单胞菌，一种革兰氏阴性厌氧菌，被鉴定为与严重， 慢性形式的牙周病，是口腔组织的成功殖民者，并且可以侵入并保留 在原代牙龈上皮细胞（GECs）中存活较长时间。牙龈卟啉单胞菌能够在细胞内 复制和调节许多表型和GECs的信号转导特性。与许多细胞内 虽然牙龈卟啉单胞菌是对它们的宿主有害的病原体，但是牙龈卟啉单胞菌不诱导GEC中的凋亡或坏死死亡。 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，抑制GECs细胞死亡信号通路的机制和关键上游信号通路的作用机制尚不清楚。 介质沿着由牙龈卟啉单胞菌诱导的生物化学和形态学改变， 表征了此外，由微生物长时间侵入GECs的后果是， 考虑到其在上皮内繁殖和传播感染的能力不断增强， 感染细胞的数量仍有待确定。 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，将通过检查细胞死亡-存活标志物和 整个感染过程中的表型事件。调节凋亡细胞的潜在机制 由牙龈卟啉单胞菌介导的应答将被表征，并且微生物的繁殖能力和 将确定随时间在上皮内的扩散及其与宿主细胞存活的关系。流式细胞术， 荧光显微镜，磷酸特异性蛋白质印迹激活试验，RNA干扰，和 将采用基于微阵列的方法来实现这些目标。 牙周病是影响美国大部分地区的最普遍的多微生物疾病之一。 这给医疗卫生系统带来了沉重的负担。此外，口腔感染相关 与牙龈卟啉单胞菌已被链接作为潜在的危险因素，以主要的系统性健康问题， 心血管疾病、糖尿病、中风和早产。对拟议目标的调查将 有助于牙龈卟啉单胞菌与宿主细胞相互作用的概念框架，并定义更多 控制牙龈卟啉单胞菌相关疾病的靶向方法。