Título:	Avaliação da atividade imunomodulatória e/ou antifúngica dos peptídeos ToAP3 e ToAP4 obtidos de escorpião e dos peptídeos Polybia-MPII e Agelaia-MPI obtidos de vespa
Autor(es):	Veloso Júnior, Paulo Henrique de Holanda
Orientador(es):	Bocca, Anamélia Lorenzetti
Assunto:	Peptídeos antimicrobianos Atividade imunomodulatória Atividade antifúngica Atividade antimicrobiana Escorpião Vespa
Data de publicação:	28-Jan-2020
Data de defesa:	18-Jun-2019
Referência:	VELOSO JÚNIOR, Paulo Henrique de Holanda. Avaliação da atividade imunomodulatória e/ou antifúngica dos peptídeos ToAP3 e ToAP4 obtidos de escorpião e dos peptídeos Polybia-MPII e Agelaia-MPI obtidos de vespa. 2019. 129 f., il. Tese (Doutorado em Patologia Molecular)—Universidade de Brasília, Brasília, 2019.
Abstract:	Antimicrobial peptides (AMPs) are small molecules found in all pluricelular organisms, which may have microbicide and immunomodulatory activity. The aim of this present work is evaluate the peptides ToAP3 and ToAP4, obtained from scorpions, and Polybia-MPII and Agelaia-MPI, obtained from wasp, activities as potential therapeutic drugs in fungal infections. In order to evaluate the immunomodulatory potential of the AMPs ToAP3 and ToAP4, bone marrow-derived macrophages (BMDMs) or bone marrow-derived dendritic cells (BMDCs) were stimulated or not with LPS, either in the presence or absence of the AMPs ToAP3 or ToAP4 to analyze its ability to modulate the cytokine and nitric oxide production. The levels of microRNA and mRNA were determined from qRT-PCR and ELISA accessed cytokine gene coding proteins. Phenotypical markers of activation and differentiation of BMDCs were verified by flow cytometry. For the antimicrobial analyses, it was evaluated the AMPs activity against the fungus Cryptococcus neoformans, verifying its minimal inhibitory concentration (MIC), the possible association between the wasp and scorpion AMPs by checkboard assay, the action mechanism of the AMPs Polybia-MPII and Agelaia-MPI by the membrane permeability to propidium iodide and atomic force microscopy, as well as the survival rate in the Galleria mellonella model. Furthermore, the AMPs Polybia-MPII and Agelaia-MPI were encapsulated in nanoparticles of PMVE/MA and their activity was accessed in vitro. The results obtained for ToAP3 and ToAP4 show that both AMPs have the capability to reduce the transcripts levels of TNF-α and IL-1β, as well as the secretion of proteins when these cells were stimulated with LPS. Analyzing the BMDCs, the AMPs reduced the secretion levels of TNF-α before and after the LPS stimulus, and this reduction was associated with the interaction with Toll-like receptor 4 (TLR-4). ToAP4 increased the expression of MHC-II molecules stimulated with LPS, and ToAP3 reduced the levels of co-stimulatory molecules. In the antimicrobial analyses, only Polybia-MPII and Agelaia-MPI were capable of acting against Cryptococcus neoformans fungus and its biofilm. Besides that, only the AMPs obtained from wasp showed additive effect when combined. The treatment with this AMPs elicited changes in the fungal membrane and morphology. These results were confirmed in in vivo assays with Galleria mellonella infected with C. neoformans. The encapsulation analyses showed that it was possible to formulate the PMVE/MA nanoparticles carried with Polybia-MPII or Agelaia-MPI AMPs, without compromise their effect against C. neoformans fungus. However, the AMPs were encapsulated in low concentrations. Altogether, these results are promising for the development of new therapies, capable of modulate the host immune response and acting against fungal infections, such as criptococcosis.
Unidade Acadêmica:	Faculdade de Medicina (FM)
Informações adicionais:	Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2019.
Programa de pós-graduação:	Programa de Pós-Graduação em Patologia Molecular
Licença:	A concessão da licença deste item refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições: Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.bce.unb.br, www.ibict.br, http://hercules.vtls.com/cgi-bin/ndltd/chameleon?lng=pt&skin=ndltd sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra disponibilizada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
Agência financiadora:	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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