Lipocalin-2 as mediator of chemokine expression and granulocyte infiltration during ischemia and reperfusion
| Autor: | Markus Kofler, Felix Aigner, Stefan Schneeberger, Stefan König, Stephan Sickinger, Jakob Troppmair, Peter Obrist, Raimund Margreiter, H. G. Schwelberger, Johann Pratschke, Philipp Schumpp, Herbert Maier, Martin Hermann, Natalie Vallant |
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| Rok vydání: | 2012 |
| Předmět: |
Chemokine
Apoptosis Myocardial Reperfusion Injury Granulocyte Mice Lipocalin-2 Gene expression Chlorocebus aethiops medicine Animals Receptor Promoter Regions Genetic Oncogene Proteins Transplantation biology Cell adhesion molecule business.industry Chemotaxis medicine.disease Lipocalins Mice Inbred C57BL medicine.anatomical_structure Neutrophil Infiltration Immunology COS Cells biology.protein Cancer research Heart Transplantation Receptors Chemokine Chemokines business Reperfusion injury Infiltration (medical) Cell Adhesion Molecules Acute-Phase Proteins |
| Zdroj: | Transplant international : official journal of the European Society for Organ Transplantation. 26(7) |
| ISSN: | 1432-2277 |
| Popis: | Lipocalin-2 (Lcn2) expression contributes to ischemia and reperfusion injury (IRI) by enhancing pro-inflammatory responses. The aim of this work was to elucidate the regulation of Lcn2 during hypoxia and its effects on the expression of key chemokines and adhesion molecules. Lcn2 wt and Lcn2(-/-) mice were used in a heterotopic heart transplantation model. Quantitative RT-PCR was applied for chemokine gene expression analysis. Reporter gene studies were used to elucidate the regulation of the Lcn2 promoter by hypoxia. HIF-1β expression led to a 2.4-fold induction of the Lcn2 promoter. Apart from an earlier onset of granulocyte infiltration in the Lcn2 wt setting after 2 h of reperfusion compared with the Lcn2(-/-) setting (P < 0.013), exogenous application of recombinant Lcn2 revealed a trend toward increase of granulocyte infiltration. Analyzed chemokines were expressed significantly higher in the Lcn2 wt setting at 2 h of reperfusion (P ≤ 0.05). The number of apoptotic cells observed in Lcn2(-/-) grafts was significantly higher than in the Lcn2 wt setting. Our results indicate that Lcn2 affects granulocyte infiltration in the reperfused graft by modulating the expression of chemokines, their receptors and the apoptotic rate. |
| Databáze: | OpenAIRE |
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