Treatment with the IDO1 inhibitor 1-MT reduced inflammatory responses in macrophages and ameliorated cardiomyocyte injury in a mouse model of chronic viral myocarditis.
Does IDO1 inhibition with 1-MT reduce inflammatory response and ameliorate cardiomyocyte injury in a mouse model of chronic viral myocarditis?
Inhibition of IDO1 with 1-MT reduces macrophage-mediated inflammation and ameliorates cardiomyocyte injury in a mouse model of viral myocarditis.
Inflammation and myocardial weakness, two major hallmarks of chronic viral myocarditis (VMC), often lead to dilated cardiomyopathy or chronic heart failure. It has been reported that indoleamine 2,3-dioxygenase-1 (IDO1) may play a pathogenic role in the progression of inflammatory diseases. Hence, the study is set out to investigate the potential role of IDO1 in chronic VMC by establishing a mouse model of VMC by intraperitoneally injected with coxsackievirus B3 (CVB3). After model establishment, the expression of IDO1 was determined by RT-qPCR and Western blot analysis. IDO1 was identified as an up-regulated gene in CVB3-induced VMC. Then, in order to elucidate the potential role of IDO1 in VMC, macrophages were isolated and treated with the overexpression plasmid of IDO1 or IDO1 inhibitor (1-MT). After that, these transfected macrophages were co-cultured with normal cardiomyocytes, followed by measurement of inflammatory factors and evaluation of cardiomyocyte injury. The overexpression of IDO1 was observed to significantly enhance the levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α), as well as lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) content. By contrast, the treatment of 1-MT in macrophages reversed the promoting effects of IDO1 on cardiomyocyte injury. Co-culture experiment showed that overexpressed IDO1 impaired cardiomyocyte, which was alleviated upon treatment of 1-MT. Taken together, the key findings of the present study provide evidence that 1-MT-mediated IDO1 suppression could potentially reduce inflammatory response in macrophages and consequently ameliorate cardiomyocyte injury in mice with VMC.
Guo et al. (Thu,) conducted a other in Chronic viral myocarditis. IDO1 inhibitor (1-MT) vs. IDO1 overexpression / Control was evaluated on Inflammatory factors (IL-6, IL-1β, TNF-α) and cardiomyocyte injury (LDH activity and MDA content). Treatment with the IDO1 inhibitor 1-MT reduced inflammatory responses in macrophages and ameliorated cardiomyocyte injury in a mouse model of chronic viral myocarditis.