MECHANISM OF LEUKOTRIENE INHIBITION BY BOTANICAL OILS

植物油抑制白三烯的机制

• 批准号: 7607701
• 负责人: FLOYD H CHILTON
• 金额: $ 18.15万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607701
• 关键词: Acids; Affect; Allergic rhinitis; Anabolism; Arachidonic Acids; Asthma; Biochemical; Borago; Botanicals; Classification; Computer Retrieval of Information on Scientific Projects Database; Disease; Enzymes; Fatty Acids; Funding; Gene Expression; Generations; Grant; Human; In Vitro; Inflammation; Inflammatory; Institution; Leukotriene Production; Leukotrienes; Measures; Metabolic; Metabolism; Oils; Pathway interactions; Prevalence; Production; Proteins; Protocols documentation; Research; Research Personnel; Resources; Source; Supplementation; Testing; United States National Institutes of Health; base; cytokine; in vivo; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is a disease that affects over 20 million people and its prevalence in the US increased by 74% from 1980 to 1995. Inhibition of leukotriene production is a proven approach for the management of asthma and allergic rhinitis. We believe that leukotriene inhibition can be optimized to achieve similar results as pharmacologic agents if the mechanism of action of fatty acids in the most efficacious oils can be determined and then fatty acids altered accordingly. This proposal takes a systematic approach to answer these questions in humans. The protocol focuses on the biochemical basis by which fatty acids inhibit leukotriene biosynthesis. Experiments are directed at measuring the in vitro and in vivo effects of these fatty acids on the production of critical intermediates in the leukotriene generation pathway and the expression of enzymes and cytokines that participate in inflammation and arachidonic acid metabolism. Two specific hypotheses are tested: 1) GLA inhibition of leukotriene generation centers around the metabolic intermediate, dihommogammalinolenic acid (DGLA) and 2) and fatty acid supplementation impacts gene expression to reduce message and protein levels of enzymes that participate in leukotriene generation. We believe these studies will increase the likelihood that botanical oils such as borage can be effectively utilized to block leukotriene generation in inflammatory diseases.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哮喘是一种影响超过 2000 万人的疾病，从 1980 年到 1995 年，其在美国的患病率增加了 74%。抑制白三烯的产生是治疗哮喘和过敏性鼻炎的行之有效的方法。我们相信，如果可以确定最有效的油中脂肪酸的作用机制，然后相应地改变脂肪酸，则可以优化白三烯抑制以获得与药物制剂相似的结果。该提案采用系统的方法来回答人类的这些问题。该协议重点关注脂肪酸抑制白三烯生物合成的生化基础。实验旨在测量这些脂肪酸对白三烯生成途径中关键中间体的产生以及参与炎症和花生四烯酸代谢的酶和细胞因子的表达的体外和体内影响。测试了两个具体假设：1) GLA 对白三烯生成的抑制以代谢中间体二高γ亚麻酸 (DGLA) 为中心，2) 脂肪酸补充会影响基因表达，从而降低参与白三烯生成的酶的信息和蛋白质水平。我们相信这些研究将增加琉璃苣等植物油被有效利用来阻止炎症性疾病中白三烯生成的可能性。