Immunosuppressive Proteins Produced by Oral Pathogens

口腔病原体产生的免疫抑制蛋白

• 批准号: 6623735
• 负责人: BRUCE J SHENKER
• 金额: $ 27.74万
• 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/6623735
• 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（由申请人提供）：在过去几年中， 近年来，对该病的病因和发病机制的研究取得了进展， 牙周病然而，免疫的性质和贡献 系统对这些疾病仍不清楚。基本假设是， 免疫系统在最小化和/或预防感染方面起主要作用。 此外，该申请假定免疫调节异常 有助于牙周病的发病机制和易感性。在 关于这一点，先前的研究表明，梭杆菌属 核密螺旋体和齿垢密螺旋体产生免疫抑制蛋白（ISP）。 所提出的研究的基本假设是， 病原体产生介导局部和/或全身免疫抑制的ISP， 从而增强它们自身的毒力和/或其它机会致病菌的毒力 微生物的我们的计划是把调查的重点放在F。具核 (Fip)和T.已显示可诱导人类的齿垢（Sip）ISP 淋巴细胞停滞在中期G1期的细胞周期。而且 初步研究确定每个ISP由两个亚基组成。的 此应用程序的目标是定义负责 ISP诱导的G1期阻滞，并确定结构与 ISP子单元的功能。该研究由四个具体目标组成：1） 确定F.核质（Fip）和 7'齿垢（Sip）ISP诱导的人淋巴细胞G1期阻滞; 2）确定 如果G1期阻滞是不可逆的，导致G1期检查点激活， 凋亡级联反应; 3）确定Fip是否存在并作为一种免疫调节剂发挥作用。 Fip A和Fip B在诱导细胞凋亡中的作用 G1阻滞;和4）为了确定是否包含G1阻滞的ISP的两种肽， 7'齿垢（Sip）是由不同的基因编码，如果是这样，以确定 每个肽的功能作用。