Gp130-dependent release of acute phase proteins is linked to the activation of innate immune signaling pathways

PLoS One. 2011 May 4;6(5):e19427. doi: 10.1371/journal.pone.0019427.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics*
  • Animals
  • Cells, Cultured
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology*
  • Interleukin-6 / pharmacology
  • Lipocalin-2
  • Lipocalins / genetics
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins / genetics
  • Polymerase Chain Reaction
  • Serum Amyloid A Protein / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics


  • Acute-Phase Proteins
  • Interleukin-6
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Saa3 protein, mouse
  • Serum Amyloid A Protein
  • Tissue Inhibitor of Metalloproteinase-1
  • Lcn2 protein, mouse
  • Cytokine Receptor gp130

Associated data

  • GEO/GSE25278