Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3.
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.
Institute of Medical Immunology and Berlin-Brandenburg Center of Regenerative Therapies, Charité Universitätsmedizin Berlin, Berlin, Germany.
Mir-Farzin
MF
Mashreghi
Roman
R
Klemz
Isabela Schmitt
IS
Knosalla
Bernhard
B
Gerstmayer
Uwe
U
Janssen
Roland
R
Buelow
Alicja
A
Jozkowicz
Jozef
J
Dulak
Hans-Dieter
HD
Volk
Katja
K
Kotsch
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011524:Protoporphyrins / Q000008:administration & dosage / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1