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

Autor(es)

Ribeiro Fernandes, Juliane Cristina ^{[1, 2]} ; Aoki, Juliana Ide ^[1] ; Acuna, Stephanie Maia ^[1] ; Zampieri, Ricardo Andrade ^[1] ; Markus, Regina P. ^[1] ; Floeter-Winter, Lucile Maria ^[1] ; Muxel, Sandra Marcia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Med Trop, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 9, MAR 20 2019.
• Citações Web of Science: 2

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. (AU)

• Processo FAPESP: 16/19815-2 - Papel dos microRNAs na resposta imune mediada por TLRs na infecção por Leishmania amazonensis.
• Beneficiário: Sandra Marcia Muxel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/03273-6 - Análise de transcriptoma de macrófagos murinos infectados com Leishmania amazonensis: análise de transcritos do parasita e hospedeiro
• Beneficiário: Juliana Ide Aoki
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/15263-4 - Alterações na composição de microRNAs em macrófagos infectados por Leishmania amazonensis
• Beneficiário: Sandra Marcia Muxel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50717-1 - Estudos bioquímicos, moleculares e funcionais da relação Leishmania-macrófago
• Beneficiário: Lucile Maria Floeter-Winter
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/23519-2 - Análise do papel de fatores de transcrição e miRNAs na regulação da expressão gênica em macrófagos murinos infectados por Leishmania amazonenses
• Beneficiário: Stephanie Maia Acuna
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto