Moran Linda B, Duke Dawn C, Graeber Manuel B
University Department of Neuropathology, Imperial College London, Faculty of Medicine, Division of Neuroscience, and Hammersmith Hospitals Trust, London, UK.
J Neuroimmunol. 2007 Feb;183(1-2):1-6. doi: 10.1016/j.jneuroim.2006.10.023. Epub 2006 Dec 22.
We have analysed the microglial pathway stimulated by interferon-gamma (IFN-gamma) using an in silico approach employing a database of eukaryotic molecular interactions and a microarray dataset validated by quantitative real-time PCR (qRT-PCR). Following IFN-gamma stimulation, production of neuroprotective factors by microglia was found to be reduced while caspase 1 and serping1 which are involved in cell death cascades are up-regulated suggesting a safeguarding mechanism. Extracellular matrix interactions and intracellular protein degradation are altered in concert with these changes. The regulatory network of IFN-gamma responsive microglial genes is outlined in detail and differentially expressed genes are mapped to their respective cellular compartments. A pathway approach to the analysis of microarray data is advocated since overlaying pathway and actual expression data as shown here greatly facilitates understanding the biological meaning of a gene regulatory network. In addition, genes of similar function that are differentially regulated are less likely to be false positives than single unrelated genes.
我们使用一个真核分子相互作用数据库和一个经定量实时聚合酶链反应（qRT-PCR）验证的微阵列数据集，通过计算机模拟方法分析了干扰素-γ（IFN-γ）刺激的小胶质细胞途径。在IFN-γ刺激后，发现小胶质细胞产生的神经保护因子减少，而参与细胞死亡级联反应的半胱天冬酶1和丝氨酸蛋白酶抑制剂1上调，提示存在一种保护机制。细胞外基质相互作用和细胞内蛋白质降解与这些变化协同改变。详细概述了IFN-γ反应性小胶质细胞基因的调控网络，并将差异表达基因映射到它们各自的细胞区室。提倡采用途径方法分析微阵列数据，因为如此处所示将途径与实际表达数据叠加，极大地有助于理解基因调控网络的生物学意义。此外，与单个不相关基因相比，功能相似但差异调节的基因不太可能是假阳性。
