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- W4313385603 abstract "Abstract Trypanosoma cruzi (T. cruzi) causes Chagas disease that is one of the most frequent causes of heart failure and sudden death in Latin America. We observed the therapeutic effect of SRT1720 and explored its immunological mechanisms especially its effect on macrophage phenotype and function in chronic Chagasic mouse. SRT1720, an SIRT1 agonist, was injected intraperitoneally in T. cruzi infected mice at 1 mg/mouse/dose during day 45–66 post-infection (pi, three times a week). Mice were harvested during chronic disease phase (~150 days pi). Left ventricular dysfunction was prevented in SIRT1720-treated chagasic mice. SRT1720 ameliorated the clinical severity of chronic Chagas diseases, decreased proinflammatory cytokine (IFN-γ, IL-1 β, TNF-α) gene expression and inflammatory infiltrate in chronic chagasic hearts. The expression of iNOS, a specific marker for M1, was decreased in SIRT1720-treated chagasic heart. Splenic evaluation by flow cytometry showed both M1 (CD80+ and CD64+) and M2 (CD200R+ and CD206+) macrophages were activated in chronically-infected mice, and SRT1720 inhibited T. cruzi -induced increase in M1 macrophages. These results demonstrated that SRT1720 has therapeutic potential in Chagas disease possibly through preventing the polarization of M1 macrophages and inhibiting inflammatory responses. In vitro experiments will be done to confirm these results. Spleen macrophages will be isolated from these mice and will be cultured for 24h. The release of NO and accumulation of iNOS and secretion of IFN-γ, IL-1 β, TNF-α in cultured macrophages will be examined." @default.
- W4313385603 created "2023-01-06" @default.
- W4313385603 creator A5022012227 @default.
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- W4313385603 date "2016-05-01" @default.
- W4313385603 modified "2023-10-16" @default.
- W4313385603 title "SRT1720 inhibition of M1 macrophages and chronic inflammation in Chagas disease" @default.
- W4313385603 doi "https://doi.org/10.4049/jimmunol.196.supp.124.3" @default.
- W4313385603 hasPublicationYear "2016" @default.
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