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.
Moran
Linda B
LB
University Department of Neuropathology, Imperial College London, Faculty of Medicine, Division of Neuroscience, and Hammersmith Hospitals Trust, London, UK.
Duke
Dawn C
DC
Graeber
Manuel B
MB
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011917:Rats, Inbred Lew
D007371:Interferon-gamma