Gutierrez Fredy Roberto Salazar, Lalu Manoj Mathew, Mariano Flávia Sammartino, Milanezi Cristiane Maria, Cena Jonathan, Gerlach Raquel Fernanda, Santos Jose Eduardo Tanus, Torres-Dueñas Diego, Cunha Fernando Queiróz, Schulz Richard, Silva João Santana
Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of Sao Paulo, Brazil.
J Infect Dis. 2008 May 15;197(10):1468-76. doi: 10.1086/587487.
The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.
克氏锥虫感染急性期心脏中发生的强烈炎症反应受到白细胞和心肌细胞产生的细胞因子和趋化因子的调节。基质金属蛋白酶（MMPs）最近已成为心血管炎症的调节因子。在本研究中，我们通过免疫组织化学分析、明胶酶谱分析、酶联免疫吸附测定和实时聚合酶链反应，对克氏锥虫感染的C57BL/6小鼠的心脏组织进行分析，研究了MMP-2和MMP-9在克氏锥虫诱导的心肌炎中的作用。感染后第14天观察到MMP-2和MMP-9的转录水平、免疫反应性和酶活性增加。与对照组相比，用MMP抑制剂治疗的小鼠心脏炎症明显减轻，寄生虫血症峰值延迟，存活率提高。在治疗组中还观察到心脏肿瘤坏死因子-α、干扰素-γ、血清亚硝酸盐和血清硝酸盐水平降低。这些结果表明MMPs在克氏锥虫诱导的急性心肌炎的诱导中起重要作用。
