title: Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress.
abstract: The multiligand receptor for advanced glycation end products (RAGE) of the Ig superfamily transduces the biological impact of discrete families of ligands, including advanced glycation end products, certain members of the S100/calgranulin family, high mobility group box-1, Mac-1 (alpha(M)beta(2), CD11b/CD18), and amyloid-beta peptide and beta-sheet fibrils. Although structurally dissimilar, at least at the monomeric level, recent evidence suggests that oligomeric forms of these RAGE ligands may be especially apt to activate the receptor and up-regulate a program of inflammatory and tissue injury-provoking genes. The challenge in probing the biology of RAGE and its impact in acute responses to stress and the potential development of chronic disease is to draw the line between mechanisms that evoke repair versus those that sustain inflammation and tissue damage. In this review, we suggest the concept that the ligands of RAGE comprise a primal program in the acute response to stress. When up-regulated in environments laden with oxidative stress, inflammation, innate aging, or high glucose, as examples, the function of these ligand families may be transformed from ones linked to rapid repair to those that drive chronic disease. Identification of the threshold beyond which ligands of RAGE mediate repair versus injury is a central component in delineating optimal strategies to target RAGE in the clinic.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Kevan
authors.initials: K
authors.lastname: Herold
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Jean
authors.initials: J
authors.lastname: Emond
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D018448:Models, Immunological; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000378:metabolism*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic