Peroxisome proliferation-activated receptor-γ ligands ameliorate experimental autoimmune myocarditis

被引:36
作者
Yuan, ZY
Liu, Y
Liu, Y
Zhang, JJ
Kishimoto, C
Wang, YN
Ma, AQ
Liu, ZQ
机构
[1] Xian Jiaotong Univ, Hosp 1, Dept Cardiovasc Med, Xian 710061, Peoples R China
[2] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto 6068501, Japan
基金
中国国家自然科学基金;
关键词
myocarditis; immunity; T cells; PPAR-gamma; cytokines;
D O I
10.1016/S0008-6363(03)00457-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been shown to ameliorate a variety of inflammatory conditions. The present study tested the hypothesis that PPAR-gamma ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation of T cells, as well as suppression of the expression of proinflammatory cytokines. Methods and results: EAM was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR-gamma ligands, 15-deoxy-Delta(12, 14)-PGJ(2) (15d-PGJ(2)) 200 mug/kg/day i.p. and pioglitazone (PIO) 10 mg/kg/day orally, were administered for 3 weeks to rats with EAM. The results showed that enhanced PPAR-gamma expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of PPAR-gamma ligands markedly reduced the severity of myocarditis, as shown by comparing the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores and microscopic scores. PPAR--y ligands suppressed myocardial mRNA expression of inflammatory cytokines and the expression of interleukin (IL)-1beta protein in rats with EAM. In addition, 15d-PGJ(2), and PIO treatment suppressed the proliferative response and nterferon-gamma production of T cell-enriched splenocytes from rats with EAM. Furthermore, the cytotoxic activity and myocardiogenic potential of these T cells were inhibited by 15d-PGJ(2) treatment. Conclusions: PPAR-gamma may play a role in the pathophysiology of EAM. PPAR-gamma ligands ameliorate the EAM associated with suppression of the expansion and activation of myocardiogenic T cells, as well as inhibition of the expression of proinflammatory cytokines. These results suggest that PPAR-gamma ligands such as 15d-PGJ(2) and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:685 / 694
页数:10
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