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Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress
Author(s) -
Herold Kevan,
Moser Bernhard,
Chen Yali,
Zeng Shan,
Yan Shi Fang,
Ramasamy Ravichandran,
Emond Jean,
Clynes Raphael,
Schmidt Ann Marie
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1206751
Subject(s) - glycation , rage (emotion) , inflammation , receptor , biology , hmgb1 , immunology , oxidative stress , microbiology and biotechnology , neuroscience , endocrinology , biochemistry
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 (α M β 2 , CD11b/CD18), and amyloid‐β peptide and β‐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.