MECHANISM OF LEUKOTRIENE INHIBITION BY BOTANICAL OILS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哮喘是一种影响超过2000万人的疾病，其在美国的患病率从1980年到1995年增加了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。我们认为，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实现与药理学试剂类似的结果。这项提议采取了一种系统的方法来回答人类的这些问题。该协议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作用。测试了两个特定的假设：1）GLA抑制白三烯生成的中心围绕代谢中间体二高γ-亚麻酸（DGLA），和2）脂肪酸补充影响基因表达以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植物油如琉璃苣油有效用于阻止炎症性疾病中白三烯生成的可能性。

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.