Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Área de Morfologia, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil.
Laboratório de Imunologia Celular, Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, FM, Universidade de Brasília, Brasília, DF 70910900, Brazil.
Int J Environ Res Public Health. 2020 Jul 6;17(13):4856. doi: 10.3390/ijerph17134856.
Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of (=), against promastigotes. However, its impact on the amastigote form of and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.
利什曼原虫是被忽视的疾病的病原体，这些疾病是全球公共卫生的一个重要问题。 和现有治疗方法的严重副作用的耐药菌株的不断出现，对利什曼病的治疗构成了重大挑战。我们之前已经报道过 phylloseptin-1（PSN-1）对 前鞭毛体的杀利什曼原虫活性，PSN-1 是在 (=) 的皮肤分泌物中发现的一种肽。然而，它对 无鞭毛体形式的影响及其对感染的巨噬细胞的影响尚不清楚。在这项工作中，我们评估了 PSN-1 对体外感染的巨噬细胞内 无鞭毛体的影响。我们评估了 PSN-1 处理后感染和未感染的巨噬细胞中过氧化氢和一氧化氮的产生，以及炎症和免疫调节标志物（TGF-β、TNF-α 和 IL-12）的水平。与未处理的细胞相比，PSN-1 处理可减少感染细胞的数量和每个细胞摄入的无鞭毛体的数量。在 32 µM（64 µg/mL）时，PSN-1 降低了感染和未感染巨噬细胞中的过氧化氢水平，而对 NO 产生或 TGF-β 释放几乎没有影响。PSN-1 对 IL-12 和 TNF-α 分泌的影响取决于其浓度，但总的来说，随着 PSN-1 浓度的增加，它们的水平趋于增加。需要进一步的体外和体内研究来阐明 PSN-1 的作用机制及其与免疫系统的相互作用，旨在开发药理学应用。
