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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / enzymology
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Cell Differentiation / drug effects
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Cell Differentiation / immunology*
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Cells, Cultured
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Coculture Techniques
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Dendritic Cells / cytology*
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Dendritic Cells / enzymology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Gene Expression Profiling
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Growth Inhibitors / administration & dosage
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Growth Inhibitors / physiology
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Heme Oxygenase-1 / biosynthesis
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Heme Oxygenase-1 / deficiency
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / physiology*
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / genetics
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MAP Kinase Signaling System / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Phosphorylation
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Protoporphyrins / administration & dosage
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Protoporphyrins / pharmacology
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STAT3 Transcription Factor / biosynthesis
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STAT3 Transcription Factor / metabolism
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STAT3 Transcription Factor / physiology*
Substances
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Growth Inhibitors
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Lipopolysaccharides
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Protoporphyrins
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STAT3 Transcription Factor
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Stat3 protein, mouse
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cobaltiprotoporphyrin
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Heme Oxygenase-1