Peroxisome Proliferator-Activated Receptor-γ Ligands Ameliorate Experimental Autoimmune Myocarditis Associated with Inhibition of Self-Sensitive T Cells
Peroxisome Proliferator-Activated Receptor-γ Ligands Ameliorate Experimental Autoimmune Myocarditis Associated with Inhibition of Self-Sensitive T Cells
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DOI：
10.1097/00005344-200406000-00017
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发表时间：
2004-06
影响因子：
3
通讯作者：
Zuyi Yuan;Yan Liu;Yu Liu;Ji-jun Zhang;C. Kishimoto;A. Ma;Zhi-quan Liu
中科院分区：
文献类型：
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作者：
Zuyi Yuan;Yan Liu;Yu Liu;Ji-jun Zhang;C. Kishimoto;A. Ma;Zhi-quan Liu
目的：最近的证据表明，过氧化物酶体增殖物激活受体-γ（过氧化物酶体增殖物激活受体-γ）在免疫系统中起负调节作用。本研究探讨了实验性自身免疫性心肌炎（EAM）中过氧化物酶体增殖物激活受体-γ（PPAR-γ）的表达及配体对EAM的影响。方法和结果：用猪心肌肌球蛋白免疫刘易斯大鼠，诱导实验性自身免疫性心肌炎。给予PPAR-γ配体15-脱氧-Δ 12，14-PGJ 2 200 μg · kg-1 · d-1 ip和吡格列酮10 mg · kg-1 · d-1口服，共3周。炎性心肌组织中PPAR-γ表达上调，炎性心肌组织中阳性细胞的核及核周区表达增强。给予PPAR-γ配体可显著降低心肌炎的严重程度，如心脏重量/体重比、心包积液评分、肉眼评分和显微镜评分所示。经PPAR-γ配体处理后，上调的PPAR-γ表达也降低。此外，PPAR-γ配体抑制EAM大鼠富含T细胞的脾细胞的增殖反应和干扰素-γ的产生。此外，这些T细胞的细胞毒活性和心肌发生潜力被抑制的PPAR-γ配体处理。结论：PPAR-γ配体通过抑制自身敏感性T细胞的扩增和活化，改善EAM。这些结果表明，PPAR-γ配体可能具有调节人类炎症性心脏病如心肌炎的潜力。
Objective: Recent evidence has suggested that peroxisome proliferator-activated receptor-γ (PPAR-γ) serves as a negative regulator in the immune system. In the present study, we investigated the expression of PPAR-γ and the effect of PPAR-γ ligands on experimental autoimmune myocarditis (EAM). Methods and Results: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR-γ ligands 15-deoxy-Δ 12,14 -PGJ2 200 μg · kg−1 · d−1 by ip and pioglitazone 10 mg · kg−1 · d−1 by oral were administered for 3 weeks. PPAR-γ expression was upregulated in myocarditis and the enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of the positive-stained cells in the inflammatory lesions. Administration of PPAR-γ 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-γ expression was also reduced by PPAR-γ ligands treatment. In addition, PPAR-γ ligands suppressed the proliferative response and interferon-γ 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-γ ligands treatment. Conclusions: PPAR-γ ligands ameliorate EAM associated with inhibition of expansion and activation of the self-sensitive T cells. These results suggest that PPAR-γ ligands may have the potential to modulate human inflammatory heart diseases as myocarditis.