RAGE mediates a novel proinflammatory axis

A central cell surface receptor for S100/calgranulin polypeptides

Marion A. Hofmann, Steven Drury, Caifeng Fu, Wu Qu, Akihiko Taguchi, Yan Lu, Cecilia Avila, Neeraja Kambham, Angelika Bierhaus, Peter Nawroth, Markus F. Neurath, Timothy Slattery, Dale Beach, John McClary, Mariko Nagashima, John Morser, David Stern, Ann Marie Schmidt

Research output: Contribution to journalArticle

1372 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)889-901
Number of pages13
JournalCell
Volume97
Issue number7
DOIs
StatePublished - Jun 25 1999
Externally publishedYes

Fingerprint

Leukocyte L1 Antigen Complex
Cell Surface Receptors
Peptides
Chemical activation
Inflammation
Lymphocytes
Delayed Hypersensitivity
Colitis
Phagocytes
Endothelium
Cues
Advanced Glycosylation End Product-Specific Receptor
Carrier Proteins
Genes
Tissue
Gene Expression
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hofmann, M. A., Drury, S., Fu, C., Qu, W., Taguchi, A., Lu, Y., ... Schmidt, A. M. (1999). RAGE mediates a novel proinflammatory axis: A central cell surface receptor for S100/calgranulin polypeptides. Cell, 97(7), 889-901. https://doi.org/10.1016/S0092-8674(00)80801-6

RAGE mediates a novel proinflammatory axis : A central cell surface receptor for S100/calgranulin polypeptides. / 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.

In: Cell, Vol. 97, No. 7, 25.06.1999, p. 889-901.

Research output: Contribution to journalArticle

Hofmann, MA, Drury, S, Fu, C, Qu, W, Taguchi, A, Lu, Y, Avila, C, Kambham, N, Bierhaus, A, Nawroth, P, Neurath, MF, Slattery, T, Beach, D, McClary, J, Nagashima, M, Morser, J, Stern, D & Schmidt, AM 1999, 'RAGE mediates a novel proinflammatory axis: A central cell surface receptor for S100/calgranulin polypeptides', Cell, vol. 97, no. 7, pp. 889-901. https://doi.org/10.1016/S0092-8674(00)80801-6
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. / RAGE mediates a novel proinflammatory axis : A central cell surface receptor for S100/calgranulin polypeptides. In: Cell. 1999 ; Vol. 97, No. 7. pp. 889-901.
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