RAGE in inflammation: a new therapeutic target?
High-molecular group box 1-protein, S100/calgranulins, advanced glycation end products (AGEs), amyloid-beta peptides and the family of beta-sheet fibrils contribute to a number of inflammatory conditions by promoting cellular dysfunction and breaking immune tolerance. The receptor of AGE (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules that acts as a pattern recognition receptor. Besides binding ligands actively participating in inflammation and immune responses, RAGE serves as an endothelial adhesion receptor for leukocyte integrins and promotes leukocyte recruitment and extravasation of infiltrating cells. Engagement of RAGE subsequently converts transient cellular stimulation into sustained cellular dysfunction driven by long-term activation of the proinflammatory nuclear factor-kappaB. Deletion of RAGE and pharmacological interventions targeting interruption of RAGE-ligand interaction suppresses inflammation and dampens tissue damage in experimental models of inflammatory disorders, thus delineating RAGE as a potential therapeutic target in inflammation.
Bierhaus
Angelika
A
Department of Medicine I, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
Stern
David M
DM
Nawroth
Peter P
PP
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D018836:Inflammation Mediators; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic