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Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis

Sepsis still represents an important clinical and economic challenge for intensive care units. Severe complications like multi-organ failure with high mortality and the lack of specific diagnostic tools continue to hamper the development of improved therapies for sepsis. Fundamental questions regard...

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Autores principales: Bopp, Christian, Bierhaus, Angelika, Hofer, Stefan, Bouchon, Axel, Nawroth, Peter P, Martin, Eike, Weigand, Markus A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374592/
https://www.ncbi.nlm.nih.gov/pubmed/18226173
http://dx.doi.org/10.1186/cc6164
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author Bopp, Christian
Bierhaus, Angelika
Hofer, Stefan
Bouchon, Axel
Nawroth, Peter P
Martin, Eike
Weigand, Markus A
author_facet Bopp, Christian
Bierhaus, Angelika
Hofer, Stefan
Bouchon, Axel
Nawroth, Peter P
Martin, Eike
Weigand, Markus A
author_sort Bopp, Christian
collection PubMed
description Sepsis still represents an important clinical and economic challenge for intensive care units. Severe complications like multi-organ failure with high mortality and the lack of specific diagnostic tools continue to hamper the development of improved therapies for sepsis. Fundamental questions regarding the cellular pathogenesis of experimental and clinical sepsis remain unresolved. According to experimental data, inhibiting macrophage migration inhibitory factor, high-mobility group box protein 1 (HMGB1), and complement factor C5a and inhibiting the TREM-1 (triggering receptor expressed on myeloid cells 1) signaling pathway and apoptosis represent promising new therapeutic options. In addition, we have demonstrated that blocking the signal transduction pathway of receptor of advanced glycation endproducts (RAGE), a new inflammation-perpetuating receptor and a member of the immunglobulin superfamily, increases survival in experimental sepsis. The activation of RAGE by advanced glycation end-products, S100, and HMGB1 initiates nuclear factor kappa B and mitogen-activated protein kinase pathways. Importantly, the survival rate of RAGE knockout mice was more than fourfold that of wild-type mice in a septic shock model of cecal ligation and puncture (CLP). Additionally, the application of soluble RAGE, an extracellular decoy for RAGE ligands, improves survival in mice after CLP, suggesting that RAGE is a central player in perpetuating the innate immune response. Understanding the basic signal transduction events triggered by this multi-ligand receptor may offer new diagnostic and therapeutic options in patients with sepsis.
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spelling pubmed-23745922008-05-09 Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis Bopp, Christian Bierhaus, Angelika Hofer, Stefan Bouchon, Axel Nawroth, Peter P Martin, Eike Weigand, Markus A Crit Care Review Sepsis still represents an important clinical and economic challenge for intensive care units. Severe complications like multi-organ failure with high mortality and the lack of specific diagnostic tools continue to hamper the development of improved therapies for sepsis. Fundamental questions regarding the cellular pathogenesis of experimental and clinical sepsis remain unresolved. According to experimental data, inhibiting macrophage migration inhibitory factor, high-mobility group box protein 1 (HMGB1), and complement factor C5a and inhibiting the TREM-1 (triggering receptor expressed on myeloid cells 1) signaling pathway and apoptosis represent promising new therapeutic options. In addition, we have demonstrated that blocking the signal transduction pathway of receptor of advanced glycation endproducts (RAGE), a new inflammation-perpetuating receptor and a member of the immunglobulin superfamily, increases survival in experimental sepsis. The activation of RAGE by advanced glycation end-products, S100, and HMGB1 initiates nuclear factor kappa B and mitogen-activated protein kinase pathways. Importantly, the survival rate of RAGE knockout mice was more than fourfold that of wild-type mice in a septic shock model of cecal ligation and puncture (CLP). Additionally, the application of soluble RAGE, an extracellular decoy for RAGE ligands, improves survival in mice after CLP, suggesting that RAGE is a central player in perpetuating the innate immune response. Understanding the basic signal transduction events triggered by this multi-ligand receptor may offer new diagnostic and therapeutic options in patients with sepsis. BioMed Central 2008 2008-01-09 /pmc/articles/PMC2374592/ /pubmed/18226173 http://dx.doi.org/10.1186/cc6164 Text en Copyright © 2008 BioMed Central Ltd
spellingShingle Review
Bopp, Christian
Bierhaus, Angelika
Hofer, Stefan
Bouchon, Axel
Nawroth, Peter P
Martin, Eike
Weigand, Markus A
Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title_full Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title_fullStr Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title_full_unstemmed Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title_short Bench-to-bedside review: The inflammation-perpetuating pattern-recognition receptor RAGE as a therapeutic target in sepsis
title_sort bench-to-bedside review: the inflammation-perpetuating pattern-recognition receptor rage as a therapeutic target in sepsis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374592/
https://www.ncbi.nlm.nih.gov/pubmed/18226173
http://dx.doi.org/10.1186/cc6164
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