Betulinic Acid Derivative BA5, Attenuates Inflammation and Fibrosis in Experimental Chronic Chagas Disease Cardiomyopathy by Inducing IL-10 and M2 Polarization

Frontiers in Immunology

Breno Cardim Barreto¹  Juliana Fraga Vasconcelos¹  Alex Cleber Improta Caria¹  Daniela Nascimento Silva¹  Iasmim Diniz Orge¹  Carolina Kymie Vasques Nonaka¹  Simone Garcia Macambira¹  Milena Botelho Pereira Soares²  Diogo Rodrigo Magalhães Moreira²  Emanuelle De Souza Santos²  Cássio Santana Meira²  José Maria Barbosa-Filho³  Renan Fernandes do Espírito Santo⁴ 

[1] Center for Biotechnology and Cell Therapy, Hospital São Rafael, Salvador, Brazil;FIOCRUZ, Gonçalo Moniz Institute, Salvador, Brazil;Laboratory of Pharmaceutical Technology, Federal University of Paraíba (UFPB), João Pessoa, Brazil;Science and Health Institute, Federal University of Bahia (UFBA), Salvador, Brazil;

关键词: Trypanosoma cruzi;    betulinic acid derivative;    immunomodulation;    chagas disease;    cardiomyopathy;   

DOI  :  10.3389/fimmu.2019.01257

来源: DOAJ

【 摘 要 】

Chronic Chagas disease cardiomyopathy (CCC) is a major cause of heart disease in Latin America and treatment for this condition is unsatisfactory. Here we investigated the effects of BA5, an amide semi-synthetic derivative betulinic acid, in a model of CCC. Mice chronically infected with T. cruzi were treated orally with BA5 (10 or 1 mg/Kg), three times per week, for 2 months. BA5 treatment decreased inflammation and fibrosis in heart sections but did not improve exercise capacity or ameliorate cardiac electric disturbances in infected mice. Serum concentrations of TNF-α, IFN-γ, and IL-1β, as well as cardiac gene expression of pro-inflammatory mediators, were reduced after BA5 treatment. In contrast, a significant increase in the anti-inflammatory cytokine IL-10 concentration was observed in BA5-treated mice in both tested doses compared to vehicle-treated mice. Moreover, polarization to anti-inflammatory/M2 macrophage phenotype was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers, such as Arg1 and CHI3 in mice treated with BA5. In conclusion, BA5 had a potent anti-inflammatory activity on a model of parasite-driven heart disease related to IL-10 production and a switch from M1 to M2 subset of macrophages.

【 授权许可】

Unknown