Contribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes.

2.50
HDL Handle:
http://hdl.handle.net/10033/24372
Title:
Contribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes.
Authors:
Klein, Christian; Medina, Eva; Sander, Leif; Dierssen, Uta; Roskams, Tania; Mueller, Werner; Trautwein, Christian; Goldmann, Oliver
Abstract:
BACKGROUND: Sepsis and septic shock caused by gram-positive bacteria have become increasingly frequent clinical problems. These conditions are accompanied by an overwhelming inflammation in which the liver plays a central role as a source and target of inflammatory mediators. Sepsis is still associated with high mortality rates, and new intervention strategies directed at ameliorating the extent of the inflammatory reaction are strongly needed. Here, we investigated whether blockage of the transducer gp130, a receptor involved in the regulation of the inflammatory response, might be useful in the treatment of experimental gram-positive sepsis. METHODS: An experimental model of gram-positive sepsis was used in which liver-specific gp130-deficient mice (FVB/n alfpCre+ gp130(LoxP/LoxP)) and wild-type mice (FVB/n gp130(LoxP/LoxP)) were intravenously infected with Streptococcus pyogenes. The following parameters were monitored: mortality, bacterial loads in systemic organs, serum inflammatory cytokine levels, and organ damage. RESULTS: We show that infected gp130-deficient mice survived significantly longer, had lower bacterial loads, and developed organ damage more slowly than infected wild-type mice. Furthermore, levels of interferon- gamma , interleukin-6, and the chemokine cytokine-induced neutrophil chemoattractant were significantly lower in gp130-deficient mice than in wild-type mice. Histopathological examination of livers showed lower amounts of neutrophil infiltration, apoptosis, and tissue damage in infected gp130-deficient mice than in wild-type mice. CONCLUSION: Our results demonstrate that the gp130 receptor is involved in the regulation of inflammation during gram-positive sepsis and that blockage of gp130 signaling in hepatocytes could constitute a novel target for adjunctive therapy in patients with sepsis.
Affiliation:
Medizinische Klinik III, University Hospital Aachen, Rheinisch-Westfalisch Techniche Hochschule Aachen, Aachen, Germany. christian.klein@dife.de
Citation:
Contribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes. 2007, 196 (5):755-62 J. Infect. Dis.
Journal:
The Journal of infectious diseases
Issue Date:
1-Sep-2007
URI:
http://hdl.handle.net/10033/24372
DOI:
10.1086/520090
PubMed ID:
17674319
Type:
Article
Language:
en
ISSN:
0022-1899
Appears in Collections:
Publications of RG Infection Immunology (INI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorKlein, Christian-
dc.contributor.authorMedina, Eva-
dc.contributor.authorSander, Leif-
dc.contributor.authorDierssen, Uta-
dc.contributor.authorRoskams, Tania-
dc.contributor.authorMueller, Werner-
dc.contributor.authorTrautwein, Christian-
dc.contributor.authorGoldmann, Oliver-
dc.date.accessioned2008-04-29T09:14:07Z-
dc.date.available2008-04-29T09:14:07Z-
dc.date.issued2007-09-01-
dc.identifier.citationContribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes. 2007, 196 (5):755-62 J. Infect. Dis.en
dc.identifier.issn0022-1899-
dc.identifier.pmid17674319-
dc.identifier.doi10.1086/520090-
dc.identifier.urihttp://hdl.handle.net/10033/24372-
dc.description.abstractBACKGROUND: Sepsis and septic shock caused by gram-positive bacteria have become increasingly frequent clinical problems. These conditions are accompanied by an overwhelming inflammation in which the liver plays a central role as a source and target of inflammatory mediators. Sepsis is still associated with high mortality rates, and new intervention strategies directed at ameliorating the extent of the inflammatory reaction are strongly needed. Here, we investigated whether blockage of the transducer gp130, a receptor involved in the regulation of the inflammatory response, might be useful in the treatment of experimental gram-positive sepsis. METHODS: An experimental model of gram-positive sepsis was used in which liver-specific gp130-deficient mice (FVB/n alfpCre+ gp130(LoxP/LoxP)) and wild-type mice (FVB/n gp130(LoxP/LoxP)) were intravenously infected with Streptococcus pyogenes. The following parameters were monitored: mortality, bacterial loads in systemic organs, serum inflammatory cytokine levels, and organ damage. RESULTS: We show that infected gp130-deficient mice survived significantly longer, had lower bacterial loads, and developed organ damage more slowly than infected wild-type mice. Furthermore, levels of interferon- gamma , interleukin-6, and the chemokine cytokine-induced neutrophil chemoattractant were significantly lower in gp130-deficient mice than in wild-type mice. Histopathological examination of livers showed lower amounts of neutrophil infiltration, apoptosis, and tissue damage in infected gp130-deficient mice than in wild-type mice. CONCLUSION: Our results demonstrate that the gp130 receptor is involved in the regulation of inflammation during gram-positive sepsis and that blockage of gp130 signaling in hepatocytes could constitute a novel target for adjunctive therapy in patients with sepsis.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCytokine Receptor gp130en
dc.subject.meshGene Deletionen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHepatocytesen
dc.subject.meshInflammationen
dc.subject.meshInterleukin-6en
dc.subject.meshMiceen
dc.subject.meshSepsisen
dc.subject.meshSignal Transductionen
dc.subject.meshStreptococcal Infectionsen
dc.subject.meshStreptococcus pyogenesen
dc.titleContribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes.en
dc.typeArticleen
dc.contributor.departmentMedizinische Klinik III, University Hospital Aachen, Rheinisch-Westfalisch Techniche Hochschule Aachen, Aachen, Germany. christian.klein@dife.deen
dc.identifier.journalThe Journal of infectious diseasesen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.