吲哚胺 2,3-双加氧酶-1 缺乏和犬尿氨酸途径抑制对鼠脑型疟疾的影响。

Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria.

机构信息

Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, University of Sydney, NSW, Australia.

出版信息

Int J Parasitol. 2009 Feb;39(3):363-70. doi: 10.1016/j.ijpara.2008.10.005. Epub 2008 Oct 25.

DOI:10.1016/j.ijpara.2008.10.005

PMID:19000912

Abstract

Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. In this study, two different approaches were used to examine the role of indoleamine 2,3-dioxygenase-1 (IDO-1) and its metabolites in the development of murine CM. Mice genetically deficient in IDO-1 were not protected against CM, but partial protection was observed in C57BL/6 mice treated with Ro 61-8048, an inhibitor of kynurenine-3-hydroxylase. This protection was associated with suppressed levels of picolinic acid (PA) within the brain, but not with changes in the levels of kynurenic acid (KA) or quinolinic acid (QA). These data suggest that although IDO-1 is not directly involved in the pathogenesis of CM in C57BL/6 mice, the production of the kynurenine pathway metabolite PA may contribute to the development of murine CM.

摘要

脑型疟疾（CM）可能是恶性疟原虫感染的致命表现。在这项研究中，采用两种不同的方法来研究色氨酸 2,3-双加氧酶-1（IDO-1）及其代谢物在小鼠 CM 发展中的作用。缺乏 IDO-1 的小鼠不能免受 CM 的侵害，但用色氨酸-3-羟化酶抑制剂 Ro 61-8048 处理的 C57BL/6 小鼠可获得部分保护。这种保护与脑内吡啶酸（PA）水平的降低有关，但与犬尿氨酸（KA）或喹啉酸（QA）水平的变化无关。这些数据表明，尽管 IDO-1 并未直接参与 C57BL/6 小鼠 CM 的发病机制，但犬尿氨酸途径代谢物 PA 的产生可能有助于小鼠 CM 的发展。