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

• Published in: PloS one Vol. 10; no. 5; p. e0125409
• Main Authors: Verinaud, Liana, Lopes, Stefanie Costa Pinto, Prado, Isabel Cristina Naranjo, Zanucoli, Fábio, Alves da Costa, Thiago, Di Gangi, Rosária, Issayama, Luidy Kazuo, Carvalho, Ana Carolina, Bonfanti, Amanda Pires, Niederauer, Guilherme Francio, Duran, Nelson, Costa, Fábio Trindade Maranhão, Oliveira, Alexandre Leite Rodrigues, Höfling, Maria Alice da Cruz, Machado, Dagmar Ruth Stach, Thomé, Rodolfo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.05.2015; Public Library of Science (PLoS)
• Subjects: Adoptive Transfer; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Arthritis; Autoimmune diseases; Bacteria; Biology; Biomarkers; Care and treatment; CD4 antigen; Chemical properties; Chromobacterium; Chronic infection; Cytokines; Cytokines - biosynthesis; Cytokines - genetics; Cytokines - metabolism; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Disease Models, Animal; Drug dosages; Encephalomyelitis, Autoimmune, Experimental - diagnosis; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - therapy; Evolution; Experimental allergic encephalomyelitis; Female; Foxp3 protein; Health aspects; Immune system; Immunization; Immunology; Immunoregulation; Indoles - pharmacology; Inflammation; Inflammation - diagnosis; Inflammation - immunology; Inflammation - metabolism; Inflammation - therapy; Inflammation Mediators - metabolism; Laboratory animals; Leukocytes; Lipopolysaccharides; Lipopolysaccharides - immunology; Lymphocyte Count; Lymphocytes; Lymphocytes T; Macrophages; Malaria; Mice; Multiple sclerosis; Nervous system; Neurosciences; Severity of Illness Index; Spleen; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transplants & implants; Tumors; Vector-borne diseases; Violacein; Violets; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125409

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.