Fig. 3

When the classical glucocorticoid receptor (GR) is unbound to its ligand, it is bound to a multiprotein complex of molecular chaperones. Upon binding to its appropriate ligand, GR undergoes conformational changes, dissociating from the molecular chaperones. As a result, its nuclear localization signal is exposed and the GR is translocated to the nucleus [17, 18]. The genomic actions of glucocorticoids include either transcriptional activation of genes or the transcriptional repression of genes. Transactivation consists of activation of glucocorticoid response elements (GREs) and transcription of anti-inflammatory and regulator proteins [19, 20]. The GR complex can also bind to GREs within the GILZ promoter, initiating the transcription of the Glucocorticoid-induced leucine zipper protein (GILZ), a mediator of glucocorticoid effects [21]. Transrepression consists of the GR complex binding to transcription factor subunits, preventing their association to DNA and their co-activators [19, 20];. Glucocorticoids (GCs) are also involved in non-genomic signaling. GCs have been shown to inhibit the GRB2-RAF-MEK1 pathway in A549 cells by blocking GRB2 recruitment [22]. The pathway leads to the downstream phosphorylation of cytosolic phospholipase A2 and consequent liberation of arachidonic acid and pro-inflammatory proteins [22, 23]. Pie charts adjacent to proteins represent the protein’s relative abundance in the periphery (blue), macula (orange), and fovea (gray) based on the mass spectrometry data provided by the Skeie and Mahajan [5] study