Mechanisms of Actions of Botanical Lipids on Effector Cells of/Joshua A. Boyce

植物脂质对 Joshua A. Boyce 效应细胞的作用机制

基本信息

批准号：
8007045
负责人：
FLOYD H CHILTON
金额：
$ 36.77万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8007045
关键词：
1-Phosphatidylinositol 3-Kinase Acids Affinity Allergic Disease Alprostadil Amplifiers Anti-Asthmatic Agents Anti-Inflammatory Agents Anti-inflammatory Antibiotic A23187 Arachidonate 5-Lipoxygenase Arachidonic Acids Asthma Attenuated Basophils Blood Blood Cells Borago Botanicals Bronchoconstrictor Agents Calcium Cells Chemicals Chemotactic Factors Complement Development Dietary Supplementation Dinoprostone Disease Echium Effector Cell Eicosanoids Eicosapentaenoic Acid Fatty Acids Fc Receptor Fish Oils Functional disorder Funding Gene Expression Generations Genetic Transcription Goals Human Human Volunteers IgE Immune In Vitro Infiltration Inflammation Inflammation Mediators Inflammatory Interleukin-10 Intervention Ionophores Lead Leukocytes Leukotriene B4 Leukotriene C4 Leukotrienes Light Linolenic Acids Lipids Mediator of activation protein Messenger RNA Molecular Mononuclear Morbidity - disease rate Nature Oils Omega-3 Fatty Acids Oral Outcome Pathway interactions Patients Peripheral Blood Mononuclear Cell Peroxisome Proliferator-Activated Receptors Phenotype Plant Roots Plasma Population Production Property Prostaglandin Production Prostaglandin-Endoperoxide Synthase Prostaglandins Protein Isoforms Regulatory T-Lymphocyte Research Role Rosa Seeds Series Signal Transduction Societies Source Supplementation Therapeutic Thromboxane A2 Translating Up-Regulation Zileuton airway inflammation base borage oil cytokine desaturase granulocyte healthy volunteer in vivo inhibitor/antagonist interleukin-23 lipid mediator macrophage mast cell monocyte neutrophil peripheral blood prevent protein expression receptor response stearidonic acid

1-Phosphatidylinositol 3-Kinase Acids Affinity Allergic Disease Alprostadil Amplifiers Anti-Asthmatic Agents Anti-Inflammatory Agents Anti-inflammatory Antibiotic A23187 Arachidonate 5-Lipoxygenase Arachidonic Acids Asthma Attenuated Basophils Blood Blood Cells Borago Botanicals Bronchoconstrictor Agents Calcium Cells Chemicals Chemotactic Factors Complement Development Dietary Supplementation Dinoprostone Disease Echium Effector Cell Eicosanoids Eicosapentaenoic Acid Fatty Acids Fc Receptor Fish Oils Functional disorder Funding Gene Expression Generations Genetic Transcription Goals Human Human Volunteers IgE Immune In Vitro Infiltration Inflammation Inflammation Mediators Inflammatory Interleukin-10 Intervention Ionophores Lead Leukocytes Leukotriene B4 Leukotriene C4 Leukotrienes Light Linolenic Acids Lipids Mediator of activation protein Messenger RNA Molecular Mononuclear Morbidity - disease rate Nature Oils Omega-3 Fatty Acids Oral Outcome Pathway interactions Patients Peripheral Blood Mononuclear Cell Peroxisome Proliferator-Activated Receptors Phenotype Plant Roots Plasma Population Production Property Prostaglandin Production Prostaglandin-Endoperoxide Synthase Prostaglandins Protein Isoforms Regulatory T-Lymphocyte Research Role Rosa Seeds Series Signal Transduction Societies Source Supplementation Therapeutic Thromboxane A2 Translating Up-Regulation Zileuton airway inflammation base borage oil cytokine desaturase granulocyte healthy volunteer in vivo inhibitor/antagonist interleukin-23 lipid mediator macrophage mast cell monocyte neutrophil peripheral blood prevent protein expression receptor response stearidonic acid

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项目摘要

Oral adminstration of borage and echium oils to subjects with asthma results in a decreased capacity for leukotriene (LT) generation by peripheral blood leukocytes. This is a potentially important outcome in terms of explaining the therapeutic benefits of botanical oils, but the mechanisms(s) responsible are not known. The major goal ofthis Project is to precisely define these mechanism(s) in human cells that are relevant to the pathophysiology of asthma. In Aim 1, we will determine whether supplementation with borage and echium oils impairs PI-3K signaling in basophils, neutrophils, and monocytes in the blood of patients with asthma, and whether this translates into diminished production of pathophysiologically important lipid mediators and cytokines. In Aim 2, we will determine whether supplementation with borage and echium oils shifts the profile of PG production by peripheral blood monocytes from PGE2 and thromboxane A2 (TXA2) (a powerful bronchoconstrictor) to PGE1, a mediator that has been proposed to have potent anti-inflammatory properties. We will also determine the dominant cyclooxygenase (COX) and PGE synthase (PGES) isoforms responsible for the generation of PGE1, and whether dietary supplementation with borage and echium oils uprgulates the expression and function of PPARy in peripheral blood monocytes due to a loss of suppressive Pl-3K/Akt signaling from endogenous PGE2. Upregulation of the expression and function of PPARy would be expected to reduce ainway inflammation in asthmatic subjects through suppression of transcription of proinflammatory cytokines. These studies will complement the studies in Project 1 (J. Parks) that focus on the ability of botanical oils to facilitate the development of a vasoprotective PPARy-driven macrophage phenotype. Lastly, in Aim 3, we will determine the anti-asthmatic potential of PGE1 and determine its receptor utilization based on its ability to "stabilize" human MOs. The latter studies are essential because of the critical nature of MC activation in both the initiation and perpetuation of airway inflammation in asthma. These studies are highly integral to the PPG as a whole, and will shed substantial light onto the mechanistic basis for the efficiacy of botanical oils in asthma and other inflammatory disorders.

对患有哮喘的受试者的口服臀部和eChium油的口服守卫导致能力下降白细胞白细胞产生白细胞（LT）。这是一个潜在的重要结果解释植物油的治疗益处，但尚不清楚所负责的机制。这个项目的主要目标是精确定义与人类细胞中的这些机制哮喘的病理生理学。在AIM 1中，我们将确定是否补充了泻湖和 echium油会损害嗜碱性粒细胞，中性粒细胞和单核细胞中的PI-3K信号，患者的血液哮喘以及这是否转化为病理生理上重要脂质的产生介质和细胞因子。在AIM 2中，我们将确定是否补充了泻湖和Echium Oils 从PGE2和Thomboxane A2（TXA2）转移外周血单核细胞的PG产生曲线（a） PGE1强大的支气管收缩仪），该调解员已被提议具有有效的抗炎作用特性。我们还将确定主要的环氧合酶（COX）和PGE合酶（PGES）同工型负责PGE1的产生，以及饮食中是否补充泻湖和Echium Oils 由于失去抑制来自内源性PGE2的PL-3K/AKT信号传导。 PPARY的表达和功能上调预计通过抑制转录的转录促炎细胞因子。这些研究将补充项目1（J。Parks）的研究，重点是植物油促进血管保护型巨噬细胞的发展的能力表型。最后，在AIM 3中，我们将确定PGE1的抗哮喘潜力并确定其受体利用基于其“稳定”人类MOS的能力。后者的研究至关重要，因为 MC激活在哮喘中气道炎症的启动和持续性中的临界性质。这些研究与整个PPG高度不可或缺，并且会给机械带来大量的光线植物油在哮喘和其他炎症性疾病中效率的基础。