Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System

Autor(es)

Thome, Rodolfo ; de Carvalho, Ana Carolina ; da Costa, Thiago Alves ; Watanabe Ishikawa, Larissa Lumi ; de Campos Fraga-Silva, Thais Fernanda ; Sartori, Alexandrina ; Rodrigues de Oliveira, Alexandre Leite ; Verinaud, Liana

• Tipo de documento: Artigo Científico
• Fonte: CNS Neuroscience & Therapeutics; v. 22, n. 8, p. 707-714, AUG 2016.
• Citações Web of Science: 5

Resumo

Background and Aims: Experimental autoimmune encephalomyelitis (EAE) is T-celldependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics. Artesunate (Art) is a semi-synthetic sesquiterpene derivative from artemisinin and has been shown to reduce the clinical signs of autoimmune disease models through mechanisms not yet understood. In this study, we aimed to evaluate whether administration of Art would ameliorate EAE. Methods and Results: C57BL6 mice were immunized with MOG(35-55) peptide to induce EAE. At the same time, Art treatment started (3 mg/kg/day via i.p.) for five consecutive days. We found that Art treatment reduced the clinical signs of EAE and that correlated with a reduced infiltration of cells in the CNS. Disease amelioration did not correlate with immunomodulation as recall responses, leukocyte subpopulations, and gene expression analysis were similar among treated and untreated mice. Ultimately, further analysis provided data indicating that a possible mechanism of action for Art is dependent on the cellular migration to the CNS. Conclusions: Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS. (AU)

• Processo FAPESP: 14/19492-3 - Influência das vias de sinalização mTOR, STAT1/3 e iNOS na atividade de células dendríticas tolerogênicas
• Beneficiário: Liana Maria Cardoso Verinaud
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• 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
• Processo FAPESP: 14/11588-1 - Investigação de um possível efeito terapêutico da administração de artesunato em camundongos portadores de Encefalomielite Autoimune Experimental
• Beneficiário: Ana Carolina de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica