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...
| 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 |
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| Format: | Artigo |
| Language: | Inglês |
| Published: |
MDPI
2020
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| Subjects: | |
| 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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| Summary: |
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. |
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