RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. |
| |
| Authors: | M A Hofmann S Drury C Fu W Qu A Taguchi Y Lu C Avila N Kambham A Bierhaus P Nawroth M F Neurath T Slattery D Beach J McClary M Nagashima J Morser D Stern A M Schmidt |
| |
| Institution: | College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. |
| |
| Abstract: | 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 (extracellular newly 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. |
| |
| Keywords: | |
|
|
