Peroxisome proliferator-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis associated with inhibition of self-sensitive T cells.

Abstract

OBJECTIVE:

Recent evidence has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPAR-gamma and the effect of PPAR-gamma ligands on experimental autoimmune myocarditis (EAM).

METHODS AND RESULTS:

Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR-gamma ligands 15-deoxy-Delta-PGJ2 200 microg x kg(-1) x d(-1) by ip and pioglitazone 10 mg x kg(-1) x d(-1) by oral were administered for 3 weeks. PPAR-gamma expression was upregulated in myocarditis and the enhanced PPAR-gamma expression was prominently stained in the nuclear and perinuclear regions of the positive-stained cells in the inflammatory lesions. Administration of PPAR-gamma ligands markedly reduced the severity of myocarditis, as indicated by the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores, and microscopic scores. The upregulated PPAR-gamma expression was also reduced by PPAR-gamma ligands treatment. In addition, PPAR-gamma ligands suppressed the proliferative response and interferon-gamma production of T cell-enriched splenocytes from rats with EAM. Furthermore, the cytotoxic activity and myocarditogenic potential of these T cells were inhibited by PPAR-gamma ligands treatment.

CONCLUSIONS:

PPAR-gamma ligands ameliorate EAM associated with inhibition of expansion and activation of the self-sensitive T cells. These results suggest that PPAR-gamma ligands may have the potential to modulate human inflammatory heart diseases as myocarditis.

• Authors: Zuyi Yuan, Yan Liu, Yu Liu, Jijun Zhang, Chiharu Kishimoto, Aiqun Ma, Zhiquan Liu
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 43 Issue 6 Pg. 868-75 (Jun 2004) ISSN: 0160-2446 [Print] United States
• PMID: 15167281 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxyprostaglandin J2
• Ligands
• Receptors, Cytoplasmic and Nuclear
• Thiazolidinediones
• Transcription Factors
• Prostaglandin D2
• Pioglitazone

Topics

• Animals
• Autoimmune Diseases (drug therapy, metabolism, prevention & control)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Ligands
• Myocarditis (drug therapy, metabolism, prevention & control)
• Myocytes, Cardiac (drug effects, metabolism)
• Pioglitazone
• Prostaglandin D2 (administration & dosage, analogs & derivatives, metabolism)
• Rats
• Rats, Inbred Lew
• Receptors, Cytoplasmic and Nuclear (biosynthesis, metabolism, physiology)
• Swine
• T-Lymphocytes (drug effects, metabolism)
• Thiazolidinediones (administration & dosage, metabolism)
• Transcription Factors (biosynthesis, metabolism, physiology)