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Pioglitazone, a peroxisome proliferator-activated receptor gamma activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance.
- Source :
-
Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2005 Feb; Vol. 38 (2), pp. 257-65. Date of Electronic Publication: 2005 Jan 20. - Publication Year :
- 2005
-
Abstract
- Objectives: The aim of this study is to investigate the effect of Peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand on experimental autoimmune myocarditis (EAM).<br />Background: Rat EAM model resembles the giant cell myocarditis in human. Recent studies have suggested that Th1 cytokines are involved in the initiation and progression of EAM, whereas Th2 cytokines are associated with the remission. PPAR gamma, which is a member of nuclear hormone receptor superfamily, has been known to affect not only glucose homeostasis but also immune responses, by regulating the Th1/Th2 balance.<br />Methods: Lewis rats were immunized with cardiac myosin and divided into three groups: Group N, normal control rats (n = 16); Group E, EAM rats (n = 17); and Group P, EAM rats treated with a PPAR gamma activator pioglitazone (n = 20).<br />Results: Cardiac dysfunction and remodeling were inhibited in Group P compared to Group E. Heart weight/body weight ratio and the degree of inflammation and fibrosis were significantly lower in Group P than in Group E. The mRNA levels of macrophage inflammatory protein-1alpha (MIP-1alpha), which plays an important role in the recruitment of inflammatory cells in the early stage of EAM, were upregulated in the heart of Group E, but not in the heart of Group P. Furthermore, the treatment with pioglitazone decreased the expression levels of proinflamatory cytokine (TNF alpha and IL-1beta) genes and Th1 cytokine (IFN-gamma) genes, and increased the expression levels of Th2 cytokine (IL-4) gene.<br />Conclusions: PPAR gamma ligands may have beneficial effects on myocarditis by inhibiting MIP-1alpha expression and modulating the Th1/Th2 balance.
- Subjects :
- Animals
Autoimmune Diseases immunology
Autoimmune Diseases physiopathology
Body Weight drug effects
Cytokines genetics
Cytokines metabolism
Disease Models, Animal
Female
Hemodynamics
Myocarditis immunology
Myocarditis metabolism
Myocarditis physiopathology
Organ Size drug effects
PPAR gamma metabolism
Pioglitazone
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Th1 Cells immunology
Th2 Cells immunology
Th2 Cells metabolism
Autoimmune Diseases pathology
Myocarditis pathology
PPAR gamma agonists
Th1 Cells drug effects
Th1 Cells metabolism
Th2 Cells drug effects
Thiazolidinediones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2828
- Volume :
- 38
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of molecular and cellular cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 15698832
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2004.11.010