Melatonin and Leishmania amazonensis Infection Altered miR-294, miR-30e, and miR-302d Impacting on Tnf, Mcp-1, and Nos2 Expression

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Arquivos
art_FERNANDES_Melatonin_and_Leishmania_amazonensis_Infection_Altered_miR294_miR30e_2019.PDF (4.88 MB)
Citações na Scopus
28
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
AOKI, Juliana Ide
ACUNA, Stephanie Maia
ZAMPIERI, Ricardo Andrade
MARKUS, Regina P.
FLOETER-WINTER, Lucile Maria
MUXEL, Sandra Marcia
Citação
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v.9, article ID 60, 15p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Leishmaniases are neglected diseases that cause a large spectrum of clinical manifestations, from cutaneous to visceral lesions. The initial steps of the inflammatory response involve the phagocytosis of Leishmania and the parasite replication inside the macrophage phagolysosome. Melatonin, the darkness-signaling hormone, is involved in modulation of macrophage activation during infectious diseases, controlling the inflammatory response against parasites. In this work, we showed that exogenous melatonin treatment of BALB/c macrophages reduced Leishmania amazonensis infection and modulated host microRNA (miRNA) expression profile, as well as cytokine production such as IL-6, MCP-1/CCL2, and, RANTES/CCL9. The role of one of the regulated miRNA (miR-294-3p) in L. amazonensis BALB/c infection was confirmed with miRNA inhibition assays, which led to increased expression levels of Tnf and Mcp-1/Ccl2 and diminished infectivity. Additionally, melatonin treatment or miR-30e-5p and miR-302d-3p inhibition increased nitric oxide synthase 2 (Nos2) mRNA expression levels and nitric oxide (NO) production, altering the macrophage activation state and reducing infection. Altogether, these data demonstrated the impact of melatonin treatment on the miRNA profile of BALB/c macrophage infected with L. amazonensis defining the infection outcome.
Palavras-chave
polyamine pathway, nitric oxide synthase, arginase 1, interleukin, mRNA-miRNA interaction, melatonin and Leishmania
URI
https://observatorio.fm.usp.br/handle/OPI/32030
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Artigos e Materiais de Revistas Científicas - IMT