Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.
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 μg 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 naïve 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.
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Liana
L
Verinaud
Department of Genetics Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Stefanie Costa Pinto
SC
Lopes
Department of Genetics Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Isabel Cristina Naranjo
IC
Prado
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Fábio
F
Zanucoli
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Thiago
T
Alves da Costa
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Rosária
R
Di Gangi
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Luidy Kazuo
LK
Issayama
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Ana Carolina
AC
Carvalho
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Amanda Pires
AP
Bonfanti
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Guilherme Francio
GF
Niederauer
Biological Chemistry Laboratory, Chemistry Institute, University of Campinas, Campinas, SP, Brazil; Laboratory of Nanostructured Synthesis and Biosystems Interactions (NanoBioss), Chemistry Institute, University of Campinas, Campinas, SP, Brazil.
Nelson
N
Duran
Department of Genetics Evolution and Bioagents, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Fábio Trindade Maranhão
FT
Costa
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Alexandre Leite Rodrigues
AL
Oliveira
Department of Histology and Embryology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Maria Alice da Cruz
MA
Höfling
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Dagmar Ruth Stach
DR
Machado
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Rodolfo
R
Thomé
D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D007211:Indoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C063155:violacein