RAGE Mediates a Novel Proinflammatory Axis
Copyright policy )RAGE Mediates a Novel Proinflammatory Axis
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.
- University of Tübingen Germany
- King’s University United States
- Columbia University United States
- University of Applied Sciences Mainz Germany
- Johannes Gutenberg University of Mainz Germany
Phagocytes, DNA, Complementary, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Receptor for Advanced Glycation End Products, S100 Proteins, Membrane Proteins, Colitis, Mice, Inbred C57BL, Jurkat Cells, Mice, Leukocytes, Mononuclear, Animals, Humans, Cattle, Female, Amino Acid Sequence, Endothelium, Vascular, Receptors, Immunologic, Peptides
Phagocytes, DNA, Complementary, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Receptor for Advanced Glycation End Products, S100 Proteins, Membrane Proteins, Colitis, Mice, Inbred C57BL, Jurkat Cells, Mice, Leukocytes, Mononuclear, Animals, Humans, Cattle, Female, Amino Acid Sequence, Endothelium, Vascular, Receptors, Immunologic, Peptides
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