6533b7cffe1ef96bd125997a
RESEARCH PRODUCT
RAGE Mediates a Novel Proinflammatory Axis
Steven DruryMarion A. HofmannTimothy SlatteryAngelika BierhausJohn McclaryDale L. BeachJohn MorserAnn Marie SchmidtMariko NagashimaNeeraja KambhamPeter P. NawrothAkihiko TaguchiCaifeng FuMarkus F. NeurathWu QuDavid M. SternCecilia AvilaYan Lusubject
endocrine system diseasesbiologyBiochemistry Genetics and Molecular Biology(all)nutritional and metabolic diseasesInflammationS100A12 ProteinGeneral Biochemistry Genetics and Molecular BiologyCell biologyRAGE (receptor)Proinflammatory cytokineCell surface receptorImmunologycardiovascular systembiology.proteinmedicineCalgranulincardiovascular diseasesmedicine.symptomSignal transductionReceptorhuman activitiesdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1999-06-01 | Cell |