ROCK inhibitor Y-27632 down-regulates Il-1β expression in mice with experimental autoimmune myocarditis

Abstract

Autoimmune myocarditis is a limited or diffuse inflammation of the myocardium brought on by dysfunction in the normal function of cellular and humoral immunity of the body. Mouse models of experimental autoimmune myocarditis (EAM) were constructed using peptide MyHC-α614–629. After secondary immunization, the mice were given intraperitoneal injection of the Rho kinase (ROCK) inhibitor Y-27632 the next day, and the heart tissues of the EAM mice were isolated and weighed on day 21. As a result, the hearts of EAM mice were significantly enlarged and whitened; the body weight (BW) of mice in the EAM group increased slowly, and the heart weight (HW) and the ratio of HW/eventual body weight (e-BW) were raised; the inflammatory infiltration and fibrosis of the myocardial tissue were aggravated. But Y-27632 treatment improved the above-mentioned phenotypic or pathological features of EAM mice. Besides, the monocytes in the spleen of EAM mice mounted up, which showed a decline in number after Y-27632 treatment. Mechanistic analysis revealed a significant increase in the expression of Notch1, Hes1, Jag2, Dil1, Tlr2 and Il-1β in the myocardial tissue of the EAM mice. Notably, the expression of IL-1β was consistent with that of Notch1 and Tlr2. After Y-27632 treatment, the expression of key target genes (Notch1, Hes1, Dil1 and Jag2) of the NOTCH signaling pathway and Tlr2 expression were obviously decreased. The ROCK inhibitor Y-27632 exerts a protective effect in EAM mice by down-regulating Il-1β expression. This study aims to provide a reference value for the future treatment of myocarditis in clinical settings.