Immunoregulatory effects of α-GalCer in a murine model of autoimmune myocarditis

• Published in: Experimental and molecular pathology 2011-10, Vol.91 (2), p.636-642
• Main Authors: Liu, Wei, Li, Shuqing, Tian, Wendan, Li, Weimin, Zhang, Zhiyi
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Biological and medical sciences; Blotting, Western; C/EBPβ; Cardiology. Vascular system; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Disease Models, Animal; Forkhead Transcription Factors - metabolism; Galactosylceramides - immunology; Galactosylceramides - pharmacology; Heart; iNKT; Interleukin-2 Receptor alpha Subunit - metabolism; Investigative techniques, diagnostic techniques (general aspects); Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Mice; MMPs; Myocarditis - immunology; Myocarditis - pathology; Myocarditis. Cardiomyopathies; Myocardium - enzymology; Myocardium - immunology; Myocardium - pathology; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Severity of Illness Index; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Tregs; α-Galactosylceramide
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2011.06.010

This study was designed to investigate the role of α-galactosylceramide (α-GalCer) on experimental autoimmune myocarditis (EAM), and to explore the underlying mechanisms. Balb/c mice were immunized with porcine cardiac myosin to establish the EAM model. All the immunized mice were divided into two groups, the α-GalCer group and the EAM group. α-GalCer or vehicle was given intraperitoneally at the time of immunization. Then α-GalCer or PBS was injected on alternate days for 6 weeks. 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 analyzed 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 other two groups. In contrast, the expression of α-SMA did not differ significantly among the three groups. This study demonstrated that α-GalCer alleviates EAM. Thus, α-GalCer represents a potential therapeutic target for autoimmune-inflammation mediated cardiac damage. α-GalCer protects EAM through upregulation of the proportion of iNKT and Tregs and increased expression of myocardial MMP-2 and MMP-9. ► Myocardial inflammation improved significantly in EAM Following α-GalCer treatment for 6 weeks. ► α-GalCer significantly increased cardiac MMP-2, -9 level, while decreased C/EBPβ expression. ► α-GalCer protects EAM through upregulation of iNKT and Tregs. ► α-GalCer represents a potential therapeutic target for cardiac inflammatory damage.