Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice

Détails

ID Serval
serval:BIB_101A14B81C1F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Interferon-gamma induces chronic active myocarditis and cardiomyopathy in transgenic mice
Périodique
American Journal of Pathology
Auteur(s)
Reifenberg  K., Lehr  H. A., Torzewski  M., Steige  G., Wiese  E., Kupper  I., Becker  C., Ott  S., Nusser  P., Yamamura  K., Rechtsteiner  G., Warger  T., Pautz  A., Kleinert  H., Schmidt  A., Pieske  B., Wenzel  P., Munzel  T., Lohler  J.
ISSN
0002-9440 (Print)
Statut éditorial
Publié
Date de publication
2007
Volume
171
Numéro
2
Pages
463-472
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines. There is unequivocal clinical and experimental evidence that the cytokine tumor necrosis factor-alpha is involved in the development of chronic heart failure, but a putative cardiotoxic potential of the proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma transgenic mice, which constitutively express IFN-gamma in their livers and hence exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice spontaneously developed chronic active myocarditis, characterized by the infiltration of not only CD4(+) and CD8(+) T cells but also Mac2(+) (galectin 3(+)) macrophages and CD11c(+) dendritic cells, eventually culminating in cardiomyopathy. Echocardiographic analyses exhibited a left ventricular dilation and impaired systolic function induced by IFN-gamma overexpression. IFN-gamma-mediated cardiotoxicity was associated with high-level cardiac transcription of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-12 and the macrophage-attracting chemokines MCP1 and MIP1-alpha. Myotoxic IFN-gamma effects could not be detected in smooth or striated muscle tissue, suggesting cardiomyocellular specificity of the toxic IFN-gamma effect. The precise mechanism of IFN-gamma cardiotoxicity remains to be elucidated
Pubmed
Web of science
Création de la notice
29/01/2008 19:33
Dernière modification de la notice
20/08/2019 13:36
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