Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells

Autor(es):Mostrar menos -

Verinaud, Liana ^[1] ; Pinto Lopes, Stefanie Costa ^[2] ; Naranjo Prado, Isabel Cristina ^[2] ; Zanucoli, Fabio ^[1] ; da Costa, Thiago Alves ^[1] ; Di Gangi, Rosaria ^[1] ; Issayama, Luidy Kazuo ^[1] ; Carvalho, Ana Carolina ^[1] ; Bonfanti, Amanda Pires ^[1] ; Niederauer, Guilherme Francio ^[1] ; Duran, Nelson ^{[3, 4]} ; Maranhao Costa, Fabio Trindade ^[2] ; Rodrigues Oliveira, Alexandre Leite ^[1] ; da Cruz Hoefling, Maria Alice ^[5] ; Stach Machado, Dagmar Ruth ^[1] ; Thome, Rodolfo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Inst Chem, Biol Chem Lab, Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Inst Chem, Lab Nanostruct Synth & Biosyst Interact NanoBioss, Campinas, SP - Brazil

^[5] Univ Estadual Campinas, Inst Biol, Dept Histol & Embryol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 5 MAY 4 2015.
• Citações Web of Science: 5

Resumo

Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola), a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 mu g of LPS and were treated with viola (3.5mg/kg) via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naive mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE)-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+ Foxp3+). We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation) and stimulation of regulatory T cells (in chronic inflammation). New studies must be conducted in order to assess the possible use of viola in therapeutic approaches in human autoimmune diseases. (AU)

• Processo FAPESP: 11/17965-3 - Efeito da atrofia tímica induzida pela infecção com Plasmodium berghei no estabelecimento e curso da encefalomielite autoimune experimental (EAE)
• Beneficiário: Liana Maria Cardoso Verinaud
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/23664-6 - Plasmodium vivax e imunopatogênese: estudo das interações entre endotélio, plaquetas e micropartículas na citoaderência parasitária
• Beneficiário: Stefanie Costa Pinto Lopes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/01892-0 - Avaliação ex-vivo dos efeitos antimaláricos da violaceína em isolados Amazônicos de Plasmodium vivax e P. falciparum e análise da sua atividade em camundongos infectados com cepas de P. chabaudi resistentes a antimaláricos
• Beneficiário: Isabel Cristina Naranjo Prado
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/02631-0 - Papel do óxido nítrico (NO) na modulação da encefalomielite autoimune experimental (EAE) após transferência adotiva de células dendríticas tolerogênicas: influência dos eixos MyD88-mTOR-iNOS e STAT1/3-iNOS
• Beneficiário: Rodolfo Thomé
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado