Regulation of Platelet-activating Factor Acetylhydrolase During Inflammation

炎症过程中血小板激活因子乙酰水解酶的调节

• 批准号: 8101574
• 负责人: KATHERINE M HOWARD
• 金额: $ 36万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8101574
• 关键词: Affect; Alveolar Bone Loss; Anti-Inflammatory Agents; Anti-inflammatory; Applications Grants; Arachidonic Acids; Biological; Calcium; Cell Line; Chronic; Communicable Diseases; Cytosolic Phospholipase A2; Data; Disease; Disease Progression; Eicosanoids; Environmental Risk Factor; Enzymes; Escherichia coli; Etiology; Exhibits; G-Protein-Coupled Receptors; Generations; Genetic; Goals; Health; Host Defense Mechanism; Human; Indium; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Inositol; Investigation; Lead; Leukocytes; Leukotriene B4; Ligands; Lipopolysaccharides; Microbe; Molecular; Oral; Pathway interactions; Periodontal Diseases; Periodontitis; Phospholipase C; Platelet Activating Factor; Platelet Activating Factor Degradation; Porphyromonas gingivalis; Production; Receptor Activation; Regulation; Research; Research Proposals; Respiratory Burst; Severity of illness; Signal Pathway; TNF gene; Testing; Tissues; Toll-Like Receptor 2; Toll-like receptors; Tumor Necrosis Factor-alpha; Up-Regulation; Vascular Permeabilities; Work; disorder risk; enzyme activity; equilibration disorder; insight; lipid mediator; microbial; novel; novel therapeutic intervention; oral bacteria; pathogen; platelet activating factor receptor; programs; response; toll-like receptor 4

DESCRIPTION (provided by applicant): Periodontitis is characterized as a chronic inflammatory disease triggered by pathogenic microbes and their products such as lipopolysaccharide.(LPS) The ensuing production of host inflammatory mediators contributes to disease progression and severity. Platelet-activating factor (PAF) is a potent inflammatory mediator that has been implicated in the progression of periodontal disease. A crucial mechanism in limiting the levels of PAF is the expression and activity of the enzyme involved in PAF degradation, PAF acetylhydrolase (PAF-AH). Our preliminary data demonstrates that PAF-AH expression is increased in response to inflammatory mediators. However, LPS isolated from the periodontal pathogen P. gingivalis may curtail this expression which could disturb the balance between PAF synthesis and degradation leading to a heightened inflammatory response. Our long-range research goals are to understand at the molecular level the dynamic relationship between inflammation and PAF-AH expression and activity as it pertains to periodontal disease. Two closely related Specific Aims will examine the regulation of PAF-AH in a human monocytic cell line in response to inflammatory mediators. Specifically, we will examine the expression and regulation of PAF-AH in response to stimulation with E. Coli LPS, two unique forms of P. gingivalis LPS, and from the inflammatory mediators PAF and TNF-1. Completion of the proposed Specific Aims will provide novel and important mechanistic information on how the host defense mechanism controls and limits inflammatory episodes. PUBLIC HEALTH RELEVANCE: Periodontitis is a chronic inflammatory disease that affects both oral and systemic health. Understanding the mechanism of regulation of an anti-inflammatory enzyme called platelet-activating factor acetylhydrolase will provide insight into the etiology of periodontal disease and potentially lead to novel therapeutic approaches.

描述（申请人提供）：牙周炎是一种由病原微生物及其产物如脂多糖引发的慢性炎症性疾病。(LPS)随后产生的宿主炎症介质有助于疾病的进展和严重程度。血小板活化因子（PAF）是一种强有力的炎症介质，与牙周病的进展有关。限制PAF水平的关键机制是参与PAF降解的酶PAF乙酰水解酶（PAF-AH）的表达和活性。我们的初步数据表明，PAF-AH的表达增加炎症介质的反应。然而，从牙周病原体牙龈卟啉单胞菌中分离的LPS可能会减少这种表达，这可能会扰乱PAF合成和降解之间的平衡，导致炎症反应加剧。我们的长期研究目标是在分子水平上了解炎症与PAF-AH表达和活性之间的动态关系，因为它与牙周病有关。两个密切相关的特定目的将检查PAF-AH在人单核细胞系中响应炎症介质的调节。具体而言，我们将研究PAF-AH在E. Coli LPS，牙龈卟啉单胞菌LPS的两种独特形式，以及来自炎症介质PAF和TNF-1。完成所提出的具体目标将提供关于宿主防御机制如何控制和限制炎症发作的新颖和重要的机制信息。 公共卫生相关性：牙周炎是一种慢性炎症性疾病，影响口腔和全身健康。了解称为血小板活化因子乙酰水解酶的抗炎酶的调节机制将提供对牙周病病因学的深入了解，并可能导致新的治疗方法。