title: Immunoregulatory effects of α-GalCer in a murine model of autoimmune myocarditis.
abstract: 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.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Harbin Medical University, 150001, China. wliu4@uvm.edu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Shuqing
authors.initials: S
authors.lastname: Li
authors.forename: Wendan
authors.initials: W
authors.lastname: Tian
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology*; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D000199:Actins; D022763:CCAAT-Enhancer-Binding Protein-alpha; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005699:Galactosylceramides; D053645:Interleukin-2 Receptor alpha Subunit; C493154:alpha-galactosylceramide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9