RAGE Mediates a Novel Proinflammatory Axis A Central Cell Surface Receptor for S100/Calgranulin Polypeptides

Autor: Hofmann, Marion A, Drury, Steven, Fu, Caifeng, Qu, Wu, Taguchi, Akihiko, Lu, Yan, Avila, Cecilia, Kambham, Neeraja, Bierhaus, Angelika, Nawroth, Peter, Neurath, Markus F, Slattery, Timothy, Beach, Dale, McClary, John, Nagashima, Mariko, Morser, John, Stern, David, Schmidt, Ann Marie
Jazyk: angličtina
Předmět:
Zdroj: Cell. (7):889-901
ISSN: 0092-8674
DOI: 10.1016/S0092-8674(00)80801-6
Popis: S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (e xtracellular n ewly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.
Databáze: OpenAIRE