Mashreghi Mir-Farzin, Klemz Roman, Knosalla Isabela Schmitt, Gerstmayer Bernhard, Janssen Uwe, Buelow Roland, Jozkowicz Alicja, Dulak Jozef, Volk Hans-Dieter, Kotsch Katja
Institute of Medical Immunology and Berlin-Brandenburg Center of Regenerative Therapies, Charité Universitätsmedizin Berlin, Berlin, Germany.
J Immunol. 2008 Jun 15;180(12):7919-30. doi: 10.4049/jimmunol.180.12.7919.
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.
单次使用钴原卟啉（CoPPIX）诱导血红素加氧酶1（HO-1）可预防同种异体移植后的炎性肝衰竭和缺血再灌注损伤。在此背景下，HO-1介导的供体来源树突状细胞成熟和迁移的抑制被认为是移植物保护的关键事件之一。为了更详细地研究CoPPIX诱导HO-1活性的鲜为人知的机制，我们对小鼠肝脏进行了基因表达分析，结果显示CoPPIX处理后STAT3上调。通过使用野生型和HO-1缺陷型树突状细胞，我们证明脂多糖诱导的成熟依赖于STAT3磷酸化且独立于HO-1活性。总之，我们的观察结果修正了我们对HO-1抗炎特性的理解，并突出了STAT3的免疫调节能力，这对于靶向包括缺血再灌注损伤在内的不良免疫反应可能具有更大的意义。
