The microglial gene regulatory network activated by interferon-gamma.

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.