Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages

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 Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatm...

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Main Authors: Kückelhaus, Selma Aparecida Souza, Aquino, Daniela Sant’Ana de, Borges, Tatiana Karla dos Santos, Moreira, Daniel Carneiro, Leite, Luciana de Magalhães, Junqueira, Maria Imaculada Muniz Barboza, Kückelhaus, Carlos S., Romero, Gustavo Adolfo Sierra, Prates, Maura Vianna, Bloch Júnior, Carlos, Leite, José Roberto de Souza de Almeida
Format: Artigo
Language: Inglês
Published: MDPI 2020
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Online Access: https://repositorio.unb.br/handle/10482/39558
https://doi.org/10.3390/ijerph17134856
https://orcid.org/0000-0002-6813-6276
https://orcid.org/0000-0003-1961-7281
https://orcid.org/0000-0002-6463-362X
https://orcid.org/0000-0002-9006-4619
https://orcid.org/0000-0003-1425-926X
https://orcid.org/0000-0003-2799-6883
https://orcid.org/0000-0002-1096-3236
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spelling ir-10482-395582020-10-19T19:02:24Z Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages Kückelhaus, Selma Aparecida Souza Aquino, Daniela Sant’Ana de Borges, Tatiana Karla dos Santos Moreira, Daniel Carneiro Leite, Luciana de Magalhães Junqueira, Maria Imaculada Muniz Barboza Kückelhaus, Carlos S. Romero, Gustavo Adolfo Sierra Prates, Maura Vianna Bloch Júnior, Carlos Leite, José Roberto de Souza de Almeida Peptídeos antimicrobianos Citocinas Leishmaniose Stress oxidativo 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 Leishmania 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 Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis 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. 2020-10-19T19:02:24Z 2020-10-19T19:02:24Z 2020-07-06 Artigo KÜCKELHAUS, Selma A. S. et al. Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages. International Journal of Environmental Research and Public Health, v. 17, n. 13, 4856, 2020. DOI:10.3390/ijerph17134856. Disponível em: https://www.mdpi.com/1660-4601/17/13/4856/html. Acesso em: 19 out. 2020. https://repositorio.unb.br/handle/10482/39558 https://doi.org/10.3390/ijerph17134856 https://orcid.org/0000-0002-6813-6276 https://orcid.org/0000-0003-1961-7281 https://orcid.org/0000-0002-6463-362X https://orcid.org/0000-0002-9006-4619 https://orcid.org/0000-0003-1425-926X https://orcid.org/0000-0003-2799-6883 https://orcid.org/0000-0002-1096-3236 Inglês Acesso Aberto © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf MDPI
institution REPOSITORIO UNB
collection REPOSITORIO UNB
language Inglês
topic Peptídeos antimicrobianos
Citocinas
Leishmaniose
Stress oxidativo
spellingShingle Peptídeos antimicrobianos
Citocinas
Leishmaniose
Stress oxidativo
Kückelhaus, Selma Aparecida Souza
Aquino, Daniela Sant’Ana de
Borges, Tatiana Karla dos Santos
Moreira, Daniel Carneiro
Leite, Luciana de Magalhães
Junqueira, Maria Imaculada Muniz Barboza
Kückelhaus, Carlos S.
Romero, Gustavo Adolfo Sierra
Prates, Maura Vianna
Bloch Júnior, Carlos
Leite, José Roberto de Souza de Almeida
Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
description 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 Leishmania 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 Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis 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.
format Artigo
author Kückelhaus, Selma Aparecida Souza
Aquino, Daniela Sant’Ana de
Borges, Tatiana Karla dos Santos
Moreira, Daniel Carneiro
Leite, Luciana de Magalhães
Junqueira, Maria Imaculada Muniz Barboza
Kückelhaus, Carlos S.
Romero, Gustavo Adolfo Sierra
Prates, Maura Vianna
Bloch Júnior, Carlos
Leite, José Roberto de Souza de Almeida
author_sort Kückelhaus, Selma Aparecida Souza
title Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
title_short Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
title_full Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
title_fullStr Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
title_full_unstemmed Phylloseptin-1 is leishmanicidal for amastigotes of Leishmania amazonensis inside infected macrophages
title_sort phylloseptin-1 is leishmanicidal for amastigotes of leishmania amazonensis inside infected macrophages
publisher MDPI
publishDate 2020
url https://repositorio.unb.br/handle/10482/39558
https://doi.org/10.3390/ijerph17134856
https://orcid.org/0000-0002-6813-6276
https://orcid.org/0000-0003-1961-7281
https://orcid.org/0000-0002-6463-362X
https://orcid.org/0000-0002-9006-4619
https://orcid.org/0000-0003-1425-926X
https://orcid.org/0000-0003-2799-6883
https://orcid.org/0000-0002-1096-3236
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score 13.657419