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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

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.

对哮喘受试者口服琉璃苣和蓝蓟油会导致哮喘患者的呼吸能力降低。外周血白细胞产生白三烯（LT）。这是一个潜在的重要成果，解释植物油的治疗益处，但负责的机制尚不清楚。该项目的主要目标是精确定义人体细胞中与以下相关的这些机制哮喘的病理生理学。在目标1中，我们将确定是否补充琉璃苣， Echium油损害了前列腺癌患者血液中嗜碱性粒细胞、中性粒细胞和单核细胞中的PI-3 K信号传导哮喘，以及这是否转化为减少生产的病理生理重要的脂质介质和细胞因子。在目标2中，我们将确定是否补充琉璃苣和蓝蓟油改变外周血单核细胞产生PG的模式，使其从PGE 2和血栓素A2（TXA 2）（a PGE 1是一种被认为具有强效抗炎作用的介质，特性.我们还将确定占主导地位的环氧合酶（考克斯）和前列腺素E合酶（PGES）亚型负责PGE 1的产生，以及是否饮食补充琉璃苣和蓝蓟油由于抑制性单核细胞增殖的丧失，来自内源性PGE 2的PI-3 K/Akt信号传导。PPARy的表达和功能的上调将预期通过抑制转录来减少哮喘患者的气道炎症促炎细胞因子这些研究将补充项目1（J. Parks）中的研究，植物油促进血管保护性PPARy驱动的巨噬细胞发育的能力表型最后，在目标3中，我们将确定PGE 1的抗哮喘潜力，并确定其在哮喘中的作用。基于其“稳定”人类MO的能力，受体利用率。后一项研究是必要的，因为 MC活化在哮喘气道炎症的发生和持续中的关键性质。这些研究是PPG作为一个整体的高度组成部分，并将揭示大量的机制，植物油在哮喘和其他炎症性疾病中有效性的基础。