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Immunodominant Stress Proteins of Porphyromonas gingivalis

牙龈卟啉单胞菌的免疫显性应激蛋白

基本信息

批准号：
7826763
负责人：
DENNIS E LOPATIN
金额：
$ 38.5万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-04-01 至 2011-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7826763
关键词：
Adult Affinity Antibodies Antibody Formation Antibody-Producing Cells Antigen Presentation Arterial Fatty Streak Arteriosclerosis Bacteria Bacterial Antigens Blood Circulation Blood Vessels Cell Surface Receptors Cells Chlamydia Chronic Chronic Disease Communicable Diseases Diagnostic Disease Foam Cells Genomics Gingivitis Goals Grant Health Heat shock proteins Heat-Shock Proteins 90 Helicobacter Infections Homologous Gene IL8 gene Immune response Immunization Immunodominant Antigens In Vitro Individual Infection Inflammatory Inflammatory Response Laboratories Lead Legionella Lesion Leukocytes Ligands Lipoprotein Receptor Literature Longitudinal Studies Mediating Michigan Microbe Modality Modeling Molecular Chaperones Natural Immunity Nature Oral health Periodontal Diseases Periodontitis Porphyromonas gingivalis Process Production Proteins Proteomics Recruitment Activity Reporting Role Sampling Serum Signal Transduction Systemic disease TLR4 gene Testing Tissues Toll-like receptors Veins Work Yersinia chemokine receptor design disorder control human disease in vivo interest mRNA Expression man microbial microorganism novel strategies novel therapeutics oral bacteria pathogen protective effect receptor receptor expression research study response scavenger receptor small molecule stress protein

项目摘要

DESCRIPTION (provided by applicant): Chaperones or heat shock proteins are found in all cells from bacteria to man and are among the most highly conserved and immunodominant molecules in nature. Originally thought to facilitate the three dimensional assembly of proteins it has become increasingly clear that these molecules have functions involving the immune response to a variety of microorganisms. In addition it has been shown that protective response to stress proteins may be involved in control of diseases like IBD, Legionella, Yersinia, Chlamydia and H. pylori infections and arteriosclerosis. The long-term goals of this work is to deliniate the mechanisms of chaperone involvement in periodontitis and periodontitis-related systemic disease and to develop strategies for medicinal treatment for those diseases. We have shown that elevated levels of antibodies to the HSP90 homolog (HtpG) of the periodontal pathogen P. gingivalis were found associated with better oral health in a group of gingivitis subjects. During our current grant we have demonstrated HtpG has the ability to induce immunomodulatory activity similar to chaperones from other bacteria associated with chronic infectious diseases. In periodontitis P. gingivalis HtpG recruits antibody producing cells to the lesion and upregulates chemokine receptors on both leukocytes and vascular cells contributing to the continuning tissue destruction. HtpG is found in circulation and CVD atheromas and can induce foam cell formation, an important step in atherosclerotic plaque formation. Antibodies to HtpG downregulate IL-8 production in both leukocytes and vein cells and may mitigate the inflammatory effects in periodontitis. This application will 1) chacterize the distinct receptor-mediated immunomodulatory activities of P. gingivalis HtpG in vitro; 2) demonstrate the same activity in vivo in periodontitis and vascular tissue by microdisection, genomic/proteomic approaches; 3) correlate serum antibodies to the presence of the molecules that drive this process. Such a demonstration will prepare the way for novel therapeutic and diagnostic modalities for both periodontitis and periodontitisrelated systemic diseases. PROJECT NARATIVE: Molecules that produce a particular class of proteins proteins in cells called chaperones can become involved in disease processes under some circumstances. Understanding the way this happens can lead to treatments for chronic diseases that are the result of long-lasting, unresolved periodontitis.

描述（由申请人提供）：分子伴侣或热休克蛋白存在于从细菌到人的所有细胞中，是自然界中最高度保守和免疫显性的分子。最初被认为是促进蛋白质的三维组装，现在越来越清楚的是，这些分子具有涉及对各种微生物的免疫应答的功能。此外，已经表明对应激蛋白的保护性应答可能参与控制疾病，如IBD、军团菌、耶尔森氏菌、衣原体和H。幽门感染和动脉硬化。这项工作的长期目标是阐明分子伴侣参与牙周炎和牙周炎相关系统性疾病的机制，并制定这些疾病的药物治疗策略。我们已经发现，在一组牙龈炎受试者中，牙周病原体牙龈卟啉单胞菌的HSP 90同源物（HtpG）抗体水平升高与口腔健康状况改善相关。在我们目前的资助期间，我们已经证明了HtpG具有诱导免疫调节活性的能力，类似于与慢性感染性疾病相关的其他细菌的分子伴侣。在牙周炎中，牙龈卟啉单胞菌HtpG将抗体产生细胞募集到病变处，并上调白细胞和血管细胞上的趋化因子受体，从而导致持续的组织破坏。在循环和CVD动脉粥样硬化中发现了HtpG，并且可以诱导泡沫细胞形成，这是动脉粥样硬化斑块形成的重要步骤。HtpG抗体下调白细胞和静脉细胞中IL-8的产生，并可能减轻牙周炎的炎症作用。本申请将1）在体外检测牙龈卟啉单胞菌HtpG的不同受体介导的免疫调节活性; 2）通过显微切割、基因组/蛋白质组学方法在牙周炎和血管组织中证明相同的体内活性; 3）将血清抗体与驱动该过程的分子的存在相关联。这种示范将为牙周炎和牙周炎相关的系统性疾病的新的治疗和诊断方式铺平道路。项目说明：在某些情况下，细胞中产生一类特殊蛋白质的分子（称为分子伴侣）可能参与疾病过程。了解这种情况发生的方式可以导致慢性疾病的治疗，这些疾病是长期未解决的牙周炎的结果。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Construction and characterization of a Porphyromonas gingivalis htpG disruption mutant.

牙龈卟啉单胞菌 htpG 破坏突变体的构建和表征。

DOI：
10.1016/s0378-1097(03)00506-8
发表时间：
2003
期刊：
FEMS microbiology letters
影响因子：
2.1
作者：
Sweier,DomenicaG;Combs,Allison;Shelburne,CharlesE;Fenno,JChristopher;Lopatin,DennisE
通讯作者：
Lopatin,DennisE

Localizing antibody-defined immunoreactivity in Porphyromonas gingivalis HtpG recognized by human serum utilizing selective protein expression.

利用选择性蛋白表达，定位人血清识别的牙龈卟啉单胞菌 HtpG 中抗体定义的免疫反应性。

DOI：
10.1016/j.jim.2003.11.009
发表时间：
2004
期刊：
Journal of immunological methods
影响因子：
2.2
作者：
Sweier,DomenicaG;Shelburne,CharlesE;Cameron,Jemiah;Lopatin,DennisE
通讯作者：
Lopatin,DennisE

Serum antibodies to Porphyromonas gingivalis chaperone HtpG predict health in periodontitis susceptible patients.

DOI：
10.1371/journal.pone.0001984
发表时间：
2008-04-23
期刊：
PloS one
影响因子：
3.7
作者：
Shelburne CE;Shelburne PS;Dhople VM;Sweier DG;Giannobile WV;Kinney JS;Coulter WA;Mullally BH;Lopatin DE
通讯作者：
Lopatin DE

Differential display analysis of Porphyromonas gingivalis gene activation response to heat and oxidative stress.

牙龈卟啉单胞菌基因激活对热和氧化应激反应的差异显示分析。