Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy.

Details

Serval ID
serval:BIB_96039EB6D1D8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy.
Journal
Circulation research
Author(s)
Blyszczuk P., Kania G., Dieterle T., Marty R.R., Valaperti A., Berthonneche C., Pedrazzini T., Berger C.T., Dirnhofer S., Matter C.M., Penninger J.M., Lüscher T.F., Eriksson U.
ISSN
1524-4571[electronic]
Publication state
Published
Issued date
2009
Volume
105
Number
9
Pages
912-920
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
RATIONALE: The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease. OBJECTIVE: The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure. METHODS AND RESULTS: Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure. CONCLUSIONS: Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy.
Keywords
Animals, Autoimmunity, Bone Marrow Transplantation, CD4-Positive T-Lymphocytes/immunology, Cardiomyopathy, Dilated/immunology, Cardiomyopathy, Dilated/pathology, Cells, Cultured, Dendritic Cells/immunology, Dendritic Cells/transplantation, Disease Models, Animal, Disease Progression, Fibroblasts/immunology, Fibrosis, Freund's Adjuvant, Green Fluorescent Proteins/genetics, Heart Failure/immunology, Heart Failure/pathology, Immunity, Innate, Interleukin-1beta/metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Myeloid Differentiation Factor 88/deficiency, Myeloid Differentiation Factor 88/genetics, Myocarditis/complications, Myocarditis/immunology, Myocardium/immunology, Myocardium/pathology, Myosin Heavy Chains/immunology, Phenotype, Receptors, Interleukin-1 Type I/genetics, Receptors, Interleukin-1 Type I/metabolism, Signal Transduction, Transplantation Chimera
Pubmed
Web of science
Create date
03/02/2010 17:24
Last modification date
20/08/2019 14:58
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