Immunosuppressive Proteins Produced by Oral Pathogens

口腔病原体产生的免疫抑制蛋白

• 批准号: 6853633
• 负责人: BRUCE J SHENKER
• 金额: $ 31.7万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853633
• 关键词: Fusobacterium nucleatum; SDS polyacrylamide gel electrophoresis; Treponema; apoptosis; autoradiography; bacterial proteins; cell cycle; cyclin dependent kinase; dimer; flow cytometry; high performance liquid chromatography; human subject; immunoprecipitation; immunosuppressive; laboratory mouse; laboratory rabbit; lymphocyte; p53 gene /protein; pathologic process; periodontium disorder; proliferating cell nuclear antigen; protein structure function; terminal nick end labeling; western blottings

DESCRIPTION (provided by applicant): Over the past several years, significant progress has been made in understanding of the etiology and pathogenesis of periodontal diseases. Nevertheless, the nature and contribution of the immune system to these disorders remain unclear. The basic hypothesis is that the immune system plays a primary role to minimize and/or prevent infection. Furthermore, the application posits that immunoregulatory abnormalities contribute to the pathogenesis of and susceptibility to periodontal disease. In this regard, the prior investigations have demonstrated that Fusobacterium nucleatum and Treponema denticola produce immunosuppressive proteins (ISPs). The fundamental hypothesis of the proposed studies is that periodontal pathogens produce ISPs that mediate local and/or systemic immunosuppression, thereby enhancing their own virulence and/or that of other opportunistic microorganisms. The plan is to focus this investigation on the F. nucleatum (Fip) and T. denticola (Sip) ISP which has been shown to induce human lymphocytes to arrest in the mid G 1 phase of the cell cycle. Moreover, the preliminary studies determined each ISP is composed of two subunits. The objectives of this application are to define the events responsible for ISP-induced G1 arrest and to determine the relationship between structure and function of the ISP subunits. The study is composed of four Specific Aims: 1) To determine the molecular mechanism(s) responsible for F. nucleatum (Fip) and 7' denticola (Sip) ISP-induced G1 arrest in human lymphocytes; 2) To determine if G1 arrest is irreversible resulting in activation of the G1 checkpoint and the apoptotic cascade; 3) To determine if Fip exists and functions as a heterodimer and examine the individual role of Fip A and Fip B in the induction of G 1 arrest; and 4) To determine if the two peptides that comprise the ISP of 7' denticola (Sip) are encoded by separate genes and, if so, to determine the functional role of each peptide.

描述(申请人提供)：在过去几年中，显著 对其病因和发病机制的认识已取得进展。 牙周病。然而，免疫的性质和贡献 对这些疾病的系统治疗仍不清楚。基本假设是 免疫系统在减少和/或预防感染方面起着主要作用。 此外，申请假定免疫调节异常 与牙周病的发病机制和易感性有关。在……里面 对此，以往的调查已经证明，梭杆菌 核藻和齿密螺旋体产生免疫抑制蛋白(ISPs)。 拟议研究的基本假设是牙周 病原体产生介导局部和/或系统免疫抑制的ISP， 从而增强了他们自己和/或其他机会主义者的毒力 微生物。计划是把这次调查的重点放在核盘藻上。 (FIP)和齿纹夜蛾(T.denticola)isp，已被证明能诱导人类 淋巴细胞停滞在细胞周期的G1中期.此外， 初步研究确定，每个isp由两个亚基组成。这个 本应用程序的目标是定义负责 Isp诱导的G1期停滞，并确定结构与 ISP子单元的功能。本研究由四个具体目标组成：1) 确定核盘藻致病的分子机制(S)和 7‘-齿状病毒(Sip)isp诱导的人淋巴细胞G1期停滞；2)确定 如果G1停滞是不可逆的，导致激活G1检查点，并且 细胞凋亡级联反应；3)确定FIP是否存在并作为 并检测Fip A和Fip B在诱导中的单独作用。 G_1期停滞；以及4)确定构成G_1期抑制蛋白的两个多肽是否 7‘齿状病毒(Sip)由不同的基因编码，如果是这样的话，确定 每种多肽的功能作用。