Immunopathogenic pathways in canine inflammatory myopathies resemble human myositis
Immunopathogenic pathways in canine inflammatory myopathies resemble human myositis
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DOI：
10.1016/j.vetimm.2006.05.005
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发表时间：
2006-09-15
影响因子：
1.8
通讯作者：
Nagaraju, Kanneboyina
中科院分区：
文献类型：
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作者：
Shelton, G. Diane;Hoffman, Eric P.;Nagaraju, Kanneboyina
由于缺乏合适的动物模型，炎症性肌病的治疗进展受到阻碍。炎症性肌病自发发生在狗身上，是一种异质性的疾病，比人类更常见。虚弱和肌肉萎缩的临床症状是可靠的，并且在组织学和免疫组织学上与人类肌炎的形式相似。本研究采用微阵列技术、实时定量PCR和免疫组织化学方法对犬炎性肌病进行了基因表达研究。一些与先天免疫和适应性免疫有关的基因被高度上调，包括那些参与巨噬细胞和树突状细胞活化和迁移以及抗原加工和递呈的基因。其他基因包括参与B细胞生长、发育、迁移和活化的基因、免疫球蛋白基因、促炎和抗炎途径的基因以及参与组织重塑的基因均上调。在先前利用微阵列技术治疗人肌炎的报道中，免疫应答中有类似途径的激活。这项研究加强了犬肌炎形式可能是人类肌炎的重要动物模型的观点，并为临床前试验中使用狗的治疗反应提供了有用的生物标志物。(c) 2006 Elsevier B.V.版权所有
Progress in the treatment of inflammatory myopathies is impeded by the lack of suitable animal models. Inflammatory myopathies occur spontaneously in the dog, are a heterogeneous group of disorders, and are more common than in humans. Clinical signs of weakness and muscle atrophy are reliably present, and there are histological and immunohistological similarities to forms of human myositis. In this study, microarray technology followed by quantitative real-time PCR and immunohistochemistry on muscle biopsy sections was used to investigate gene expression in cases of canine inflammatory myopathies. Several genes involved with innate and adaptive immunity were highly upregulated including those that participate in macrophage and dendritic cell activation and migration, and antigen processing and presentation. Other genes including those that participate in B cell growth, development, migration and activation, immunoglobulin genes, genes in pro-inflammatory and anti-inflammatory pathways, and genes involved with tissue remodeling were upregulated. In previous reports utilizing microarray technology in human myositis, there was activation of similar pathways involved in the immune response. This study strengthens the argument that forms of canine myositis may be important animal models of human myositis and suggests useful biomarkers for therapeutic response using the dog in pre-clinical trials. (c) 2006 Elsevier B.V. All rights reserved.