title: 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).
  
  
  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.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, Shaanxi, China. zuyiyuan@mail.xjtu.edu.cn
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Jijun
authors.initials: J
authors.lastname: Zhang
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kishimoto
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D013552:Swine; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
chemical_list: C477819:15-deoxyprostaglandin J2; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D015230:Prostaglandin D2; D000077205:Pioglitazone