TGF-ß Signalling Regulates Cytokine Production in Inflammatory Cardiac Macrophages during Experimental Autoimmune Myocarditis.
Int J Mol Sci
; 25(11)2024 May 21.
Article
em En
| MEDLINE
| ID: mdl-38891767
ABSTRACT
Myocarditis is characterized by an influx of inflammatory cells, predominantly of myeloid lineage. The progression of myocarditis to a dilated cardiomyopathy is markedly influenced by TGF-ß signalling. Here, we investigate the role of TGF-ß signalling in inflammatory cardiac macrophages in the development of myocarditis and post-inflammatory fibrosis. Experimental autoimmune myocarditis (EAM) was induced in the LysM-Cre × R26-stop-EYFP × Tgfbr2-fl/fl transgenic mice showing impaired TGF-ß signalling in the myeloid lineage and the LysM-Cre × R26-stop-EYFP control mice. In EAM, immunization led to acute myocarditis on day 21, followed by cardiac fibrosis on day 40. Both strains showed a similar severity of myocarditis and the extent of cardiac fibrosis. On day 21 of EAM, an increase in cardiac inflammatory macrophages was observed in both strains. These cells were sorted and analysed for differential gene expression using whole-genome transcriptomics. The analysis revealed activation and regulation of the inflammatory response, particularly the production of both pro-inflammatory and anti-inflammatory cytokines and cytokine receptors as TGF-ß-dependent processes. The analysis of selected cytokines produced by bone marrow-derived macrophages confirmed their suppressed secretion. In conclusion, our findings highlight the regulatory role of TGF-ß signalling in cytokine production within inflammatory cardiac macrophages during myocarditis.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Camundongos Transgênicos
/
Transdução de Sinais
/
Citocinas
/
Fator de Crescimento Transformador beta
/
Macrófagos
/
Miocardite
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Polônia