Timing of Expression of Inflammatory Mediators in Skeletal Muscles from Mice Acutely Infected with the RA Strain of Trypanosoma cruzi
Timing of Expression of Inflammatory Mediators in Skeletal Muscles from Mice Acutely Infected with the RA Strain of Trypanosoma cruzi
复制标题
DOI：
10.1159/000218333
复制
发表时间：
2009-01-01
期刊：
影响因子：
5
通讯作者：
Santiago Corral, Ricardo
中科院分区：
文献类型：
--
作者：
Andrea Cutrullis, Romina;Postan, Miriam;Santiago Corral, Ricardo
目的：恰加斯病是由肌肉细胞中持续的克氏锥虫感染引起的，最终导致慢性炎症和组织破坏。本研究的目的是确定不同的趋化因子及其受体的表达，以及促炎细胞因子和诱导型一氧化氮合酶，从小鼠肌肉急性感染T。克鲁兹研究方法：用组织学、半定量逆转录聚合酶链反应和免疫组织化学方法对感染T. cruzi，RA菌株。结果如下：CCL 5/CCR 5和CXCL 9/CXCR 3以及iNOS、IFN-γ、TNF-α和MIF的肌肉mRNA表达的早期诱导被证明伴随着寄生和白细胞募集的进行性增加。MIF和CCL 5/CCR 5的蛋白质过表达也在感染的肌肉中得到证实。结论：急性T。在cruzi RA感染的小鼠中，促炎趋化因子、趋化因子受体、细胞因子和iNOS的基因表达上调与寄生虫负荷和肌病改变的严重程度相关。与心脏相比，横纹肌在整个急性感染过程中表现出不同的几种炎症介质表达时间。我们的研究结果表明，这些因子的早期产生增加可能有助于T。cruzi依赖性骨骼肌炎性损伤。版权所有（C）2009 S. Karger AG，巴塞尔
Objective: Chagas' disease is caused by persistent Trypanosoma cruzi infection in muscle cells that ultimately results in chronic inflammation and tissue destruction. The goal of this study was to determine the expression of different chemokines and their receptors, as well as proinflammatory cytokines and inducible nitric oxide synthase, in muscles from mice acutely infected with T. cruzi. Methods: Histological, semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemical studies were performed on skeletal muscle and myocardium of BALB/c mice infected with T. cruzi, RA strain. Results: Early induction of muscular mRNA expression for CCL5/CCR5 and CXCL9/CXCR3, as well as for iNOS, IFN-gamma, TNF-alpha and MIF, was demonstrated accompanied by progressive increases in parasitism and leukocyte recruitment. Protein overexpression for MIF and CCL5/CCR5 was also verified in the infected muscles. Conclusions: In muscles from acutely T. cruzi RA-infected mice, upregulated gene expression of proinflammatory chemokines, chemokine receptors, cytokines and iNOS is associated with the severity of parasite burden and myopathic alterations. Compared to the heart, striated muscles displayed differential timing of expression of several inflammatory mediators throughout acute infection. Our findings suggest that enhanced early production of these factors could contribute to T. cruzi-dependent inflammatory damage to skeletal muscles. Copyright (C) 2009 S. Karger AG, Basel