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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哮喘是一种影响2000多万人的疾病，从1980年到1995年，美国的哮喘患病率增加了74%。抑制白三烯的产生是治疗哮喘和过敏性鼻炎的有效方法。我们相信，如果能够确定最有效的油中脂肪酸的作用机制，然后脂肪酸相应地改变，那么白三烯的抑制可以得到优化，以达到与药物类似的结果。这项建议采取了一种系统的方法来回答人类的这些问题。该方案侧重于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在体外和体内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影响。检验了两个特定的假说：1)GLA对白三烯产生的抑制集中在代谢中间产物重高马林烯酸(DGLA)和2)补充脂肪酸影响基因表达，以降低参与白三烯产生的酶的消息和蛋白质水平。我们相信，这些研究将增加植物油，如琉璃苣，可以有效地利用来阻止炎症疾病中白三烯的产生。