Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism
Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism
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DOI：
10.1111/jpi.12279
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发表时间：
2015-11-01
影响因子：
10.3
通讯作者：
Markus, Regina P.
中科院分区：
文献类型：
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作者：
Laranjeira-Silva, Maria Fernanda;Zampieri, Ricardo A.;Markus, Regina P.
细菌或真菌引起的急性炎症反应会阻碍啮齿动物松果体的夜间褪黑激素合成。在这里，我们证明利什曼原虫感染不会损害仓鼠每日褪黑激素的节律。值得注意的是，在夜间感染的仓鼠中，用鲁津多阻断褪黑激素受体，可以减轻寄生虫负担和病变进展，而在光照阶段进行褪黑激素治疗则可以减轻利什曼原虫感染。体外研究证实了体内观察结果。褪黑激素治疗降低了巨噬细胞 Cat-2b、Cat1 和 ArgI 的表达，这些基因涉及精氨酸摄取和多胺合成。事实上，褪黑激素使巨噬细胞对精氨酸的摄取减少了 40%。补充腐胺可以恢复褪黑激素对感染性的减弱作用，表明其作用是由于寄生虫复制的抑制。这项研究表明，利什曼原虫/宿主的相互作用根据夜间松果体合成的褪黑激素以昼夜节律方式变化。我们的结果提供了有关利什曼原虫感染性的新数据，并展示了在利什曼病治疗中应用褪黑激素受体激动剂的新方法。
Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of Cat-2b, Cat1, and ArgI, genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania/host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy.