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    Faculty of Life Science, University of Manchester, Manchester

    Gp130-Dependent Release of Acute Phase Proteins Is Linked to the Activation of Innate Immune Signaling Pathways

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    Background: Elevated levels of acute phase proteins (APP) are often found in patients with cardiovascular diseases. In a previous study, we demonstrated the importance of the IL-6-gp130 axis -as a key regulator of inflammatory acute phase signaling in hepatocytes-for the development of atherosclerosis. Background/Principal Findings: Gp130-dependent gene expression was analyzed in a previously established hepatocyte-specific gp130 knockout mouse model. We performed whole transcriptome analysis in isolated hepatocytes to measure tissue specific responses after proinflammatory stimulus with IL-6 across different time points. Our analyses revealed an unexpected small gene cluster that requires IL-6 stimulus for early activation. Several of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response. Furthermore, we identified a potential biomarker Lipocalin (LCN) 2 for the gp130 dependent early inflammatory response. Conclusions/Significance: Our findings suggest a complex network of tightly linked genes involved in the early activation of different parts of the innate immune response including acute phase proteins, complement and coagulation cascade.

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    Description

    Title : Gp130-Dependent Release of Acute Phase Proteins Is Linked to the Activation of Innate Immune Signaling Pathways
    Author(s) : Maren Luchtefeld, Christoph Preuss, Frank Rühle, Eskindir P. Bogalle, Anika Sietmann, Stefanie Figura, Werner Müller, Karsten Grote, Bernhard Schieffer, Monika Stoll
    Abstract : Background: Elevated levels of acute phase proteins (APP) are often found in patients with cardiovascular diseases. In a previous study, we demonstrated the importance of the IL-6-gp130 axis -as a key regulator of inflammatory acute phase signaling in hepatocytes-for the development of atherosclerosis. Background/Principal Findings: Gp130-dependent gene expression was analyzed in a previously established hepatocyte-specific gp130 knockout mouse model. We performed whole transcriptome analysis in isolated hepatocytes to measure tissue specific responses after proinflammatory stimulus with IL-6 across different time points. Our analyses revealed an unexpected small gene cluster that requires IL-6 stimulus for early activation. Several of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response. Furthermore, we identified a potential biomarker Lipocalin (LCN) 2 for the gp130 dependent early inflammatory response. Conclusions/Significance: Our findings suggest a complex network of tightly linked genes involved in the early activation of different parts of the innate immune response including acute phase proteins, complement and coagulation cascade.
    Keywords : acute phase proteins, acute phase proteins genetics, animals, cells, cultured, cytokine receptor gp130, cytokine receptor gp130 genetics, cytokine receptor gp130 metabolism, enzyme linked immunosorbent assay, gene expression profiling, hepatocytes, hepato

    Subject : unspecified
    Area : Other
    Language : English
    Year : 2011

    Affiliations Faculty of Life Science, University of Manchester, Manchester
    Editors : Jeffrey A Gold
    Journal : PLoS ONE
    Volume : 6
    Issue : 5
    Publisher : Public Library of Science
    Pages : e19427 -
    Url : http://dx.plos.org/10.1371/journal.pone.0019427
    Doi : 10.1371/journal.pone.0019427

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