Figure 6

Model of glucocorticoid (GC) actions in the airways epithelium. Simplified (A) and detailed (B) model of PPAR-mediated anti-inflammatory actions of GC in lung epithelial cells. Following activation by allergens, TLRs activate the type 1 interferon pathway. Interferons induce the expression of inflammatory genes mediated by phosphorylated STAT1 and IRF9 transcription factors. GC treatment represses the interferon pathway via two potential mechanisms. First, upregulation (orange boxes) of RXRA and PPARGC1A enhances the activity of the PPAR pathway, which inhibits STAT1 phosphorylation, repressing interferon signaling. Secondly, down-regulation (blue boxes) of STAT1 and IRF9, reduces the amount of the transcriptional complex responsible for interferon-regulated gene expression. Clear arrowheads indicate phosphorylation. Solid arrowheads indicate activation. A dashed line represents transcriptional regulation (arrow: activation; T: repression).