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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 10, n. 5 MAY 4 2015.
• Web of Science Citations: 5

Abstract

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)

• FAPESP's process: 11/17965-3 - Effect of thymic atrophy induced by Plasmodium berghei infection in the establishment and course of experimental autoimmune encephalomyelitis (EAE)
• Grantee: Liana Maria Cardoso Verinaud
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/23664-6 - Plasmodium vivax and immunopathogenesis: study of interactions between endothelium, platelets and microparticles in parasite cytoadherence
• Grantee: Stefanie Costa Pinto Lopes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/01892-0 - Evaluation of violacein antimalarial effect on Plasmodium vivax and P. falciparum isolates from Brazilian Amazon and analysis of violacein activity on P. chabaudi multi-drug resistant infected mice
• Grantee: Isabel Cristina Naranjo Prado
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/02631-0 - Role of nitric oxide (NO) in the modulation of experimental autoimmune encephalomyelitis (EAE) after the adoptive transfer of tolerogenic dendritic cells: influence of the MyD88-mTOR-iNOS and STAT1/3-iNOS axis
• Grantee: Rodolfo Thomé
• Support Opportunities: Scholarships in Brazil - Post-Doctoral