%0 Journal Article
%T Network analysis identifies a putative role for the PPAR and type 1 interferon pathways in glucocorticoid actions in asthmatics
%A Diego Diez
%A Susumu Goto
%A John V Fahy
%A David J Erle
%A Prescott G Woodruff
%A £¿sa M Wheelock
%A Craig E Wheelock
%J BMC Medical Genomics
%D 2012
%I BioMed Central
%R 10.1186/1755-8794-5-27
%X Gene expression data were used to generate a co-transcriptional network, which was interrogated to identify modules of functionally related genes. In parallel, expression data were mapped to the human protein-protein interaction (PPI) network in order to identify modules with differentially expressed genes. A common pathways approach was applied to highlight genes and pathways functionally relevant and significantly altered following GC treatment.Co-transcriptional network analysis identified pathways involved in inflammatory processes in the epithelium of asthmatics, including the Toll-like receptor (TLR) and PPAR signaling pathways. Analysis of the PPI network identified RXRA, PPARGC1A, STAT1 and IRF9, among others genes, as differentially expressed. Common pathways analysis highlighted TLR and PPAR signaling pathways, providing a link between general inflammatory processes and the actions of GCs. Promoter analysis identified genes regulated by the glucocorticoid receptor (GCR) and PPAR pathways as well as highlighted the interferon pathway as a target of GCs.Network analyses identified known genes and pathways associated with inflammatory processes in the airway epithelium of asthmatics. This workflow illustrated a hypothesis generating experimental design that integrated multiple analysis methods to produce a weight-of-evidence based approach upon which future focused studies can be designed. In this case, results suggested a mechanism whereby GCs repress TLR-mediated interferon production via upregulation of the PPAR signaling pathway. These results highlight the role of interferons in asthma and their potential as targets of future therapeutic efforts.
%K Asthma
%K Inflammation
%K Glucocorticoids
%K Fluticasone propionate
%K Flovent
%K Network analysis
%K PPAR pathway
%K Toll-like receptor pathway
%K Interferon pathway
%U http://www.biomedcentral.com/1755-8794/5/27/abstract