Contribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
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.
AffiliationMedizinische Klinik III, University Hospital Aachen, Rheinisch-Westfalisch Techniche Hochschule Aachen, Aachen, Germany. email@example.com
The following license files are associated with this item:
- Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis.
- Authors: Mees ST, Toellner S, Marx K, Faendrich F, Kallen KJ, Schroeder J, Haier J, Kahlke V
- Issue date: 2009 Dec
- Glycoprotein 130-dependent pathways in host hepatocytes are important for liver repopulation in mice.
- Authors: Tschaharganeh DF, Kaldenbach M, Erschfeld S, Tischendorf JJ, Trautwein C, Streetz KL
- Issue date: 2010 Jan
- Lack of glycoprotein 130/signal transducer and activator of transcription 3-mediated signaling in hepatocytes enhances chronic liver injury and fibrosis progression in a model of sclerosing cholangitis.
- Authors: Plum W, Tschaharganeh DF, Kroy DC, Corsten E, Erschfeld S, Dierssen U, Wasmuth H, Trautwein C, Streetz KL
- Issue date: 2010 May
- Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function.
- Authors: Sander LE, Sackett SD, Dierssen U, Beraza N, Linke RP, Müller M, Blander JM, Tacke F, Trautwein C
- Issue date: 2010 Jul 5
- STAT3 is required for IL-6-gp130-dependent activation of hepcidin in vivo.
- Authors: Pietrangelo A, Dierssen U, Valli L, Garuti C, Rump A, Corradini E, Ernst M, Klein C, Trautwein C
- Issue date: 2007 Jan