Mono-macrophage-Derived MANF Alleviates Bacterial Myocarditis by Inhibiting NF-kappaB Activation and Myocardial Inflammation.

Abstract

Bacterial myocarditis is a key cause leading to myocardial damage and cardiac dysfunction. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been found to be an anti-inflammatory factor. This study is to explore the effect of MANF on LPS-induced myocardial inflammation and macrophage differentiation. The myocarditis mouse model was constructed by LPS treatment. Myocardial damage and serum inflammatory factors were evaluated by ELISA. RT-qPCR was used to detect mRNA of M1/M2 macrophage markers. Western blot, immunohistochemical, and immunofluorescent staining were used to examine myocardial M1/M2 macrophages and NF-κB activation. Mono-macrophage-derived MANF deficiency enhanced LPS-induced inflammatory response and increased M1 macrophages in myocardium tissues, further causing more severe myocardial injury and lower survival rate of mice. Also, LPS-induced myocardial NF-κB activation was strengthened after mono-macrophage-derived MANF knockout. Mono-macrophage-derived MANF inhibits bacterial myocarditis and myocardial M1 macrophage differentiation, which is potential to be used for bacterial myocarditis treatment clinically.