RAGE regulation and signaling in inflammation and beyond

RAGE is a key molecule in the onset and sustainment of the inflammatory response. New studies indicate that RAGE might represent a new link between the innate and adaptive immune system. RAGE belongs to the superfamily of Ig cell-surface receptors and is expressed on all types of leukocytes promoting activation, migration, or maturation of the different cells. RAGE expression is prominent on the activated endothelium, where it mediates leukocyte adhesion and transmigration. Moreover, proinflammatory molecules released from the inflamed or injured vascular system induce migration and proliferation of SMCs. RAGE binds a large number of different ligands and is therefore considered as a PRR, recognizing a structural motif rather than a specific ligand. In this review, we summarize the current knowledge about the signaling pathways activated in the different cell types and discuss a potential activation mechanism of RAGE, as well as putative options for therapeutic intervention.