COBRE: UOK HSC: P1: MICROBIAL MEDIATORS OF TISSUE CELL BEHAVIOR

COBRE：UOK HSC：P1：组织细胞行为的微生物介质

• 批准号: 7610544
• 负责人: JOHN J DMYTRYK
• 金额: $ 22.38万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610544
• 关键词: Actinobacillus; Bacteria; Cells; Clinical; Collagen; Computer Retrieval of Information on Scientific Projects Database; Computer-Assisted Image Analysis; Connective Tissue; Connective Tissue Cells; Cultured Cells; Defensins; Epithelial; Epithelial Cells; Extracellular Matrix Proteins; Fibroblasts; Funding; Gender; Gingiva; Goals; Grant; In Vitro; Institution; Measures; Mediator of activation protein; Metabolism; Microbial Biofilms; Minority; Modeling; Necrotizing Ulcerative Gingivitis; Organism; Periodontal Diseases; Periodontic specialty; Periodontitis; Periodontium; Production; Prostaglandins; Proteins; Research; Research Personnel; Resources; Signal Transduction; Signaling Molecule; Source; Testing; Time; Tissues; United States National Institutes of Health; Video Microscopy; behavior influence; cell behavior; cell motility; cytokine; microbial; migration; monolayer; oral bacteria; surgery material; therapeutic target; time use; wound

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this proposed subproject is to further our understanding of how oral bacteria and their products directly influence the behavior of tissue cells within the periodontium, specifically gingival epithelial cells and connective tissue fibroblasts. The central hypothesis to be tested in this Subproject is that biofilm bacteria exert direct effects on tissue cell behavior within the periodontium. Our specific aims are: 1) to analyze the effects of mediators produced by Actinobacillus actinomycemcomitans (Aa) (released from planktonic or biofilm associated organisms) and microbial-induced mediators (epithelial defensins and supernatants from bacteria stimulated cell cultures) on the migration and proliferation of gingival epithelial cells and fibroblasts; and 2) to determine the effects of Aa-produced mediators and microbial-induced host tissue cell mediators on the synthesis of extracellular matrix proteins, cytokines and other cell signaling molecules by gingival epithelial cells and fibroblasts. Motility of gingival epithelial cells and fibroblasts will be analyzed using time-lapse videomicroscopy and computer-assisted image analysis. Cell migration and proliferation will be studied using an in-vitro wound model, in which a confluent monolayer of epithelial cells and fibroblasts is wounded and repopulation of the created wound space is measured over time. Synthetic activities of cells will be analyzed for production of collagen and non-collagen proteins, prostaglandins, cytokines, defensins, and defensin-like molecules. Although defensins have not been been detected in fibroblasts, this has not been adequately studied in situations where bacteria are in direct contact with connective tissues for extended periods of time. This is relevant to several clinical situations in periodontics, for example, exposed surgical materials, and in certain periodontal diseases characterized by bacterial invasion into gingival connective tissue, such as aggressive periodontitis and necrotizing ulcerative gingivitis. Collectively, this group of studies will further our understanding of the the effects of bacterial biofilms on epithelial and connective tissue cell behavior and metabolism in periodontal diseases and will pave the way for further studies focusing on how these pathogenic mechanisms may become targets for therapeutic intervention.We expect no changes in the gender/minority composition of the subjects.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该提出的次要注射的总体目标是进一步了解口服细菌及其产物如何直接影响牙周内组织细胞的行为，特别是牙龈上皮细胞和结缔组织成纤维细胞。在此次次审查中要检验的中心假设是生物膜细菌对牙周内组织细胞行为产生直接影响。我们的具体目的是：1）分析放线杆菌放线菌菌（AA）产生的介质的影响（根据浮游物或生物膜相关的生物）和微生物诱导的介体（上皮性防御素和细菌刺激细胞培养物的上清液）对迁移和富属植物的迁移症和富属植物的迁移症和富含的杂物; 2）为了确定AA产生的介质和微生物诱导的宿主组织细胞介体对通过牙龈上皮细胞和成纤维细胞合成细胞外基质蛋白，细胞因子和其他细胞信号分子的影响。牙龈上皮细胞和成纤维细胞的运动性将使用延时视频显微镜和计算机辅助图像分析进行分析。细胞迁移和增殖将使用体外伤口模型进行研究，其中汇合单层的上皮细胞和成纤维细胞受伤，并随着时间的推移测量了引起的伤口空间。将分析细胞的合成活性，以生产胶原蛋白和非胶原蛋白，前列腺素，细胞因子，防御素和防御素样分子。尽管在成纤维细胞中尚未检测到防御素，但在细菌长时间与结缔组织直接接触的情况下，尚未对此进行充分的研究。这与牙周地区的几种临床情况有关，例如暴露的手术材料，以及某些以细菌侵袭牙龈结缔组织的特征的牙周疾病，例如侵袭性牙周炎和坏死性溃疡性牙龈炎。总的来说，这组研究将进一步了解细菌生物膜对牙周疾病中上皮和结缔组织细胞行为和代谢的影响，并将为进一步的研究铺平道路，以关注这些致病机制可能如何成为治疗性干预的靶标。我们期望对受试者的性别/少数群体组成不变。