Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hoetzenecker, K; Zimmermann, M; Hoetzenecker, W; Schweiger, T; Kollmann, D; Mildner, M; Hegedus, B; Mitterbauer, A; Hacker, S; Birner, P; Gabriel, C; Gyöngyösi, M; Blyszczuk, P; Eriksson, U; Ankersmit, HJ.
Mononuclear cell secretome protects from experimental autoimmune myocarditis.
Eur Heart J. 2015; 36(11):676-685
Doi: 10.1093/eurheartj/ehs459
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- Co-Autor*innen der Med Uni Graz
- GABRIEL Christian
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- Abstract:
- Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antibodies - pharmacology
- Apoptosis - physiology
- Autoantibodies - metabolism
- Autoimmune Diseases - prevention & control
- CD4-CD8 Ratio -
- CD4-Positive T-Lymphocytes - physiology
- CD40 Ligand - immunology
- CD8-Positive T-Lymphocytes - physiology
- Caspase Inhibitors - pharmacology
- Cell Proliferation - physiology
- Cells, Cultured -
- Cytokines - metabolism
- Dendritic Cells - physiology
- Disease Models, Animal -
- Fas Ligand Protein - immunology
- Humans -
- Mice, Inbred BALB C -
- Myocarditis - prevention & control
- Myosin Heavy Chains - pharmacology
- Receptors, TNF-Related Apoptosis-Inducing Ligand - immunology
- Spleen - cytology
- Find related publications in this database (Keywords)
- Myocarditis
- Conditioned medium
- Secretome
- Mononuclear cells