Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-κB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation
| Autor: | Udo S. Gaipl, Ludwig Keilholz, Franz Rödel, Claus Rödel, Reinhard E. Voll, Gianni Capalbo, Guido Hildebrandt, Benjamin Frey |
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| Rok vydání: | 2010 |
| Předmět: |
Blotting
Western Anti-Inflammatory Agents Apoptosis X-Linked Inhibitor of Apoptosis Protein Caspase 3 Inhibitor of apoptosis Peripheral blood mononuclear cell Cell Line chemistry.chemical_compound Radiation Ionizing Humans Radiology Nuclear Medicine and imaging Secretion biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling NF-kappa B Endothelial Cells Dose-Response Relationship Radiation NF-κB Hematology Transforming growth factor beta Molecular biology XIAP Oncology chemistry Cancer research biology.protein |
| Zdroj: | Radiotherapy and Oncology. 97:346-351 |
| ISSN: | 0167-8140 |
| DOI: | 10.1016/j.radonc.2010.01.013 |
| Popis: | Background and purpose This study aimed to characterize a link between X-linked inhibitor of apoptosis protein (XIAP) expression, apoptosis induction, Nuclear Factor kappa B (NF-κB) activity and the anti-inflammatory properties of low-dose ionising-radiation (LD-RT). Material and methods EA.hy.926 endothelial cells (ECs) were irradiated with doses ranging from 0.3 to 3Gy, and subsequently stimulated by TNF-α, and XIAP expression was either detected by immunoblotting or TaqMan-PCR. Apoptosis was quantified by AnnexinV staining or by caspase 3/7 activity assays. NF-κB transcriptional activity was analysed by a luciferase reporter assay, secretion of Transforming Growth Factor beta 1 (TGF-β 1 ) and adhesion of peripheral blood mononuclear cells (PBMC) to EC were quantified using ELISA and adhesion assays. Results LD-RT of the activated EA.Hy.926 EC induces XIAP expression in a discontinuous manner with a relative maximum at 0.5Gy and 3Gy which parallels a discontinuity in apoptosis induction and caspase 3/7 activity. siRNA-mediated attenuation of XIAP resulted in an increased rate of apoptosis, a hampered NF-κB transcriptional activity and a diminished secretion of TGF-β 1 . As compared to control-siRNA treated cells, adhesion of PBMC to EC was increased in XIAP depleted EA.Hy.926 EC. Conclusion The modulation of apoptosis, NF-κB activity and TGF-β 1 by XIAP in irradiated and subsequent stimulated EC contributes to an impaired PBMC/EC adhesion and to the anti-inflammatory properties of LD-RT. |
| Databáze: | OpenAIRE |
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