Article Text

PDF

Organic cardiovascular disease (myocarditis, cardiomyopathy, congenital heart disease, rheumatic heart disease,valve)
Immunoregulatory effects of α-GalCer in a murine model of autoimmune myocarditis
  1. Li Shuqing
  1. Department of Cardiology, The First Affiliated Hospital, Harbin Medical University

Abstract

Objective This study was designed to investigate the immunoregulatory role of α-galactosylceramide (α-GalCer), a ligand for invariant natural killer T (iNKT) cells, on experimental autoimmune myocarditis (EAM) induced in Balb/c mice, and to explore the underlying mechanisms of its action.

Methods Balb/c mice were immunised on day 0 with porcine cardiac myosin to establish the EAM model. All the immunised mice were divided into two groups, the α-GalCer treated group and the EAM group. A dose of α-GalCer (2 μg/mouse/injection) or vehicle (1% phosphate-buffered saline, PBS) was given intraperitoneally at the time of immunisation, and then α-GalCer or PBS was injected on alternate days for 6 weeks. Untreated Balb/c mice (n=10) served as normal controls.

Results All animals were euthanised 1 day after the last injection. Myocardial inflammation was evaluated by H & E staining and the expression levels of C/EBPβ and α-SMA were determined by immunohistochemistry. CD4 CD25 Foxp3+ Tregs and iNKT cells were analysed and sorted by flow cytometry. Western blot analysis was performed to detect MMP-2 and MMP-9 protein expression. Following α-GalCer treatment for 6 weeks, myocardial inflammation improved significantly in the α-GalCer treated group compared to the EAM group. The proportions of CD4 CD25 Foxp3+ regulatory T cells and NK1.1+ iNKT cells were statistically increased in the α-GalCer treated group compared to the EAM and normal control groups. In contrast to the EAM group, α-GalCer treatment significantly increased myocardial MMP-2 and MMP-9 expression. Expression of C/EBPβ increased significantly in the EAM group compared to the α-GalCer treated group and the normal control group. In contrast, the expression of α-SMA in the myocardium did not differ significantly among the three groups.

Conclusion This study demonstrated that α-GalCer alleviates experimental autoimmune myocarditis in Balb/c mice. Thus, α-GalCer represents a potential therapeutic target for autoimmune-inflammation mediated cardiac damage. This study revealed that α-GalCer protects experimental autoimmune myocarditis through upregulation of the proportion of iNKT and Tregs and increased expression of myocardial MMP-2 and MMP-9.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.