Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis.

Abstract:

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 microg/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-gamma 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 interferon-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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Yuan Z,Liu Y,Liu Y,Zhang J,Kishimoto C,Wang Y,Ma A,Liu Z

doi

10.1016/s0008-6363(03)00457-7

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

685-94

issue

3

eissn

0008-6363

issn

1755-3245

pii

S0008636303004577

journal_volume

59

pub_type

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