Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3

J Immunol. 2008 Jun 15;180(12):7919-30. doi: 10.4049/jimmunol.180.12.7919.

Abstract

The induction of heme oxygenase 1 (HO-1) by a single treatment with cobalt protoporphyrin (CoPPIX) protects against inflammatory liver failure and ischemia reperfusion injury after allotransplantation. In this context, the HO-1-mediated inhibition of donor-derived dendritic cell maturation and migration is discussed as one of the key events of graft protection. To investigate the poorly understood mechanism of CoPPIX-induced HO-1 activity in more detail, we performed gene expression analysis in murine liver, revealing the up-regulation of STAT3 after CoPPIX treatment. By using wild-type and HO-1-deficient dendritic cells we demonstrated that LPS-induced maturation is dependent on STAT3 phosphorylation and independent of HO-1 activity. In summary, our observations revise our understanding of the anti-inflammatory properties of HO-1 and highlight the immunomodulatory capacity of STAT3, which might be of further interest for targeting undesired immune responses, including ischemia reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / enzymology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / cytology*
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Expression Profiling
  • Growth Inhibitors / administration & dosage
  • Growth Inhibitors / physiology
  • Heme Oxygenase-1 / biosynthesis
  • Heme Oxygenase-1 / deficiency
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / physiology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Protoporphyrins / administration & dosage
  • Protoporphyrins / pharmacology
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / metabolism
  • STAT3 Transcription Factor / physiology*

Substances

  • Growth Inhibitors
  • Lipopolysaccharides
  • Protoporphyrins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • cobaltiprotoporphyrin
  • Heme Oxygenase-1