Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactions
Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactions
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DOI：
10.1096/fj.01-0306fje
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发表时间：
2001-09-01
期刊：
影响因子：
4.8
通讯作者：
Wynn, TA
中科院分区：
文献类型：
--
作者：
Hoffmann, KF;McCarty, TC;Wynn, TA
极化免疫反应的发展控制着对许多微生物的抵抗力和敏感性。然而，对几种传染性、过敏性和自身免疫性疾病的研究表明，如果不加以控制，慢性1型和2型细胞因子反应也可以导致显著的发病率和死亡率。我们使用小鼠cDNA微阵列对两种不同但同样致命的肝脏病理形式的基因表达模式进行了分子表型分析，这两种类型的肝脏病理在感染曼氏血吸虫的小鼠中发展为极化的1型和2型细胞因子反应。等级聚类分析确定了至少三组与极化的2型反应相关的基因，其中两组与极端的1型细胞因子表型相关。基因芯片研究产生的关于肝纤维化、细胞凋亡以及粒细胞募集和激活的预测后来被传统的生物学检测证实。这些数据表明，cDNA微阵列不仅有助于确定协调基因表达谱，而且对疾病组织的分子指纹识别也是非常有效的。此外，它们还说明了全基因组方法对调控传染病发病机制的分子和生化机制产生全面看法的潜力。
Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis.