title: Gp130-dependent release of acute phase proteins is linked to the activation of innate immune signaling pathways.
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.
  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
  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.
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Luchtefeld
authors.forename: Christoph
authors.initials: C
authors.lastname: Preuss
authors.forename: Frank
authors.initials: F
authors.lastname: Rühle
authors.forename: Eskindir P
authors.initials: EP
authors.lastname: Bogalle
authors.forename: Anika
authors.initials: A
authors.lastname: Sietmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Figura
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D019715:Tissue Inhibitor of Metalloproteinase-1; C071332:Lcn2 protein, mouse; D050822:Cytokine Receptor gp130