Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

Autor(es)

Andreia Vieira Pereira ^[1] ; Gustavo de Barros ^[2] ; Erika Gracielle Pinto ; Andre Gustavo Tempone ^[4] ; Ricardo de Oliveira Orsi ; Lucilene Delazari dos Santos ; Sueli Calvi ; Rui Seabra Ferreira Jr ; Daniel Carvalho Pimenta ^[9] ; Benedito Barraviera

Afiliação do(s) autor(es)

^[1] São Paulo State University. Botucatu Medical School - Brasil

^[2] São Paulo State University. Botucatu Medical School - Brasil

^[4] Adolfo Lutz Institute. Department of Parasitology - Brasil

^[9] Butantan Institute. Laboratory of Biochemistry and Biophysics - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 22, 2016-02-19.

Resumo

Abstract Background Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases. Methods Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined. Results Promastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL−1 and 1.4 μg.mL−1, respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL−1. Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H2O2. Conclusions The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect. (AU)

• Processo FAPESP: 11/23236-4 - Toxinas animais nativas e recombinantes: análise funcional, estrutural e molecular
• Beneficiário: Suely Vilela
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/53846-9 - EMU: aquisição de cromatógrafo líquido de alta eficiência (CLAE) preparativo para purificação e isolamento de serinoproteinases para produção do selante de fibrina
• Beneficiário: Benedito Barraviera
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários