P.gingivalis interactions with gingival epithelial cells

牙龈卟啉单胞菌与牙龈上皮细胞的相互作用

• 批准号: 8773766
• 负责人: Richard J Lamont
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8773766
• 关键词: Actins; American; Bacterial Infections; Biological; CXCL10 gene; Cell Communication; Cells; Disease; Ensure; Epithelial Cells; Equilibrium; Family; Generations; Gingiva; Goals; Health Status; Healthcare Systems; Human; IL8 gene; Immune; Instruction; Knowledge; LIMK1 gene; Lead; Life; Mediating; Microbe; Molecular Analysis; Natural Immunity; Oral cavity; Organism; Outcome; Pathway interactions; Periodontal Diseases; Phosphoric Monoester Hydrolases; Phosphotransferases; Porphyromonas gingivalis; Production; Regulation; Role; Serine; Signal Transduction; Signal Transduction Pathway; T-Lymphocyte; Therapeutic Agents; actin depolymerizing proteins; cell motility; cellular imaging; chemokine; cofilin; design; novel; pathogen; response

Periodontal diseases are one of the most common bacterial infections of humans and impose a significant burden on the health care system. One of the predominant pathogens in periodontal disease is P. gingivalis; however, P. gingivalis can also inhabit the oral cavity in the absence of disease. The interaction between P. gingivalis and gingival epithelial cells makes a significant contribution to the degree of equilibrium between host and microbe, and to overall gingival health status. P. gingivalis can manipulate epithelial cell signal transduction pathways in order to direct entry into the host cell and to reprogram host innate immunity. One of the effector molecules of P. gingivalis is the HAD family serine phosphatase, SerB. The goal of this proposal is define the outcomes of the interaction between P. gingivalis and gingival epithelial cells as they relate colonization of the organism and the generation of immune dysbiosis. We shall also continue our major focus on the role of the functionally versatile SerB invasin and modulin of P. gingivalis. Cofilin, an actin depolymerizing protein, is required for P. gingivalis invasion. We will examine the ability of SerB to dephosphorylate and inactivate LIMK kinase which will lead to activation of cofilin. We will then investigate the impact of P. gingivalis on ROCK, PAK1 and MK2 pathways that lead to activation of LIMK. These interactions will be observed within the cell by live cell imaging. P..gingivalis can suppress IL-8 production in part through regulation of actin dynamics. We shall study the cofilin dependent, actin mediated suppression of IL-8 by P. gingivalis. The immune disruptive ability of P. gingivalis also extends to T-cell chemokines, and the mechanism of suppression of IP-10, ITAC and Mig will be studied. We will also begin to assess biological relevance by examining T-cell migration in response to epithelial cells infected with P. gingivalis. These studies will provide a detailed molecular analysis of the targeting of host signal transduction by P. gingivalis along with the role of a specific effector phosphatase. Ultimately, the knowledge gained could be developed into strategies that could be utilized to intervene in the P. gingivalis-epithelial cell interaction to ensure that the outcome is non-harmful to the host. RELEVANCE (See instructions): P. gingivalis is a cause of periodontal diseases that afflict millions of Americans. In this study we will examine the interactions between P. gingivalis and the human cells that are colonized by the organism. The information to be gathered could be used to identify targets for novel therapeutic agents designed to interfere with the colonization and survival strategies of P. gingivalis.

牙周疾病是人类最常见的细菌感染之一，并施加了显着的 医疗保健系统负担。牙周疾病中主要病原体之一是P。 牙龈但是，牙龈疟原虫也可以在没有疾病的情况下居住口腔。相互作用 在牙龈疟原虫和牙龈上皮细胞之间，对程度做出了重大贡献 宿主和微生物之间的平衡，以及牙龈健康状况的整体。牙龈疟疾可以操纵 上皮细胞信号转导途径，以直接进入宿主细胞并重新编程宿主 先天免疫。牙龈疟原虫的效应分子之一是HAT家族丝氨酸磷酸酶，Serb。 该提案的目的是定义牙龈疟原虫与牙龈之间相互作用的结果 上皮细胞与生物体的定殖和免疫营养不良的产生。我们将 同样，我们继续关注P。 牙龈。 Cofilin是一种肌动蛋白解聚蛋白，是牙龈疟原虫侵袭所必需的。我们将检查 SERB能够去磷酸化和灭活limk激酶的能力，这将导致Cofilin的激活。我们 然后将研究牙龈疟原虫对岩石，PAK1和MK2途径的影响，从而导致激活 肢体。这些相互作用将通过活细胞成像在细胞中观察到。 p..ganivalis可以抑制 IL-8的部分产生部分通过调节肌动蛋白动力学。我们将研究Cofilin依赖性肌动蛋白 牙龈疟原虫对IL-8的介导。牙龈疟原虫的免疫破坏能力也延伸到 将研究T细胞趋化因子以及IP-10，ITAC和MIG的抑制机理。我们也会 通过检查感染的上皮细胞来检查T细胞迁移来评估生物学相关性 与牙龈疟原虫。这些研究将对宿主信号的靶向提供详细的分子分析 牙龈疟原虫的转导以及特定效应子磷酸酶的作用。最终， 获得的知识可以发展为可以用来干预P的策略。 牙龈上的上皮细胞相互作用，以确保结果对宿主无害。 相关性（请参阅说明）： 牙龈疟原虫是牙周疾病的原因，遭受了数百万美国人的困扰。在这项研究中，我们将 检查牙龈假单胞菌与被生物体定植的人类细胞之间的相互作用。这 可以收集的信息可用于识别旨在的新型治疗剂的目标 干扰牙龈疟原虫的殖民化和生存策略。