Título:	Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking
Autor(es):	Veloso Júnior, Paulo Henrique de Holanda Simon, Karina Smidt Castro, Raffael Júnio Araújo de Coelho, Luísa Coutinho Hurtado Erazo, Fabián Andrés Souza, Adolfo Carlos Barros de Neves, Rogério Coutinho das Lozano, Viviane Furlan Schwartz, Elisabeth Nogueira Ferroni Tavares, Aldo Henrique Fonseca Pacheco Mortari, Márcia Renata Kipnis, Ana Paula Junqueira Pereira, Ildinete Silva Bocca, Anamélia Lorenzetti
Assunto:	Anti-inflamatórios Células dendríticas Macrófagos Escorpião - veneno
Data de publicação:	2022
Editora:	Elsevier
Referência:	VELOSO JÚNIOR, Paulo Henrique de Holanda et al. Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking, Biomedicine & Pharmacotherapy, v. 118, 109152, 2019. DOI: https://doi.org/10.1016/j.biopha.2019.109152. Disponível em: https://www.sciencedirect.com/science/article/pii/S0753332219322346. Acesso em: 1 jun. 2022.
Abstract:	Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides’ activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1β transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies.
Licença:	© 2019 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license
DOI:	https://doi.org/10.1016/j.biopha.2019.109152
Versão da editora:	https://www.sciencedirect.com/science/article/pii/S0753332219322346
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