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.

牙周病是人类最常见的细菌感染之一， 加重了医疗保健系统的负担。牙周病的主要致病菌之一是P。 牙龈卟啉单胞菌;然而，牙龈卟啉单胞菌也可以在没有疾病的情况下栖息在口腔中。的相互作用 牙龈卟啉单胞菌和牙龈上皮细胞之间的相互作用对牙龈卟啉单胞菌的感染程度有显著影响。 宿主和微生物之间的平衡，以及整体牙龈健康状况。牙龈卟啉单胞菌可以操纵 上皮细胞信号转导途径，以便直接进入宿主细胞并重新编程宿主细胞 先天免疫牙龈卟啉单胞菌的效应分子之一是HAD家族丝氨酸磷酸酶SerB。 本提案的目的是确定牙龈卟啉单胞菌和牙龈之间相互作用的结果 上皮细胞，因为它们涉及生物体的定殖和免疫生态失调的产生。我们将 也继续我们的主要重点是功能多功能的SerB侵袭素和P的调制蛋白的作用。 牙龈炎Cofilin是一种肌动蛋白解聚蛋白，是牙龈卟啉单胞菌侵袭所必需的。我们将研究 SerB去磷酸化能力和导致cofilin活化的EPLIMK激酶。我们 然后将研究牙龈卟啉单胞菌对ROCK，PAK 1和MK 2通路的影响，这些通路导致激活 林克。将通过活细胞成像在细胞内观察这些相互作用。P...牙龈炎可以抑制 IL-8的产生部分通过调节肌动蛋白动力学。我们将研究依赖于cofilin的肌动蛋白， 牙龈卟啉单胞菌介导的IL-8抑制。牙龈卟啉单胞菌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的抑制机制。我们还将 开始通过检查T细胞响应感染的上皮细胞的迁移来评估生物学相关性 牙龈卟啉单胞菌这些研究将为宿主信号的靶向提供详细的分子分析 通过牙龈卟啉单胞菌沿着转导，并具有特异性效应磷酸酶的作用。最终 所获得的知识可以发展成可以用来干预体育运动的策略。 牙龈-上皮细胞相互作用，以确保结果对宿主无害。 相关性（参见说明）： P.牙龈炎是困扰数百万美国人的牙周病的原因。在这项研究中，我们将 检查牙龈卟啉单胞菌和被该生物体定殖的人类细胞之间的相互作用。的 所收集的信息可用于鉴定新治疗剂的靶点， 干扰牙龈卟啉单胞菌的定植和生存策略。