Inhibition of dendritic cell maturation and function is independent of heme oxygenase 1 but requires the activation of STAT3 |
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| Authors: | Mashreghi Mir-Farzin Klemz Roman Knosalla Isabela Schmitt Gerstmayer Bernhard Janssen Uwe Buelow Roland Jozkowicz Alicja Dulak Jozef Volk Hans-Dieter Kotsch Katja |
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| Affiliation: | Institute of Medical Immunology and Berlin-Brandenburg Center of Regenerative Therapies, Charité Universit?tsmedizin Berlin, Berlin, Germany. |
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| 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. |
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