| Irradiation leads to susceptibility of hepatocytes to TNF-alpha mediated apoptosis. | |
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MedLine Citation:
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PMID: 15450727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: The pathogenesis of radiation-induced-liver-disease (RILD) is still unknown. We tested the hypothesis that irradiated liver macrophages influence the viability of radiation stressed hepatocytes. PATIENTS AND METHODS: Hepatocytes and liver macrophages were isolated from rat liver, cultured and irradiated with doses of 2, 8, and 25 Gy. Cell viability was measured by trypan blue exclusion, and by annexin V/propidium iodide staining. TNF-alpha in the supernatants from liver macrophage cell culture was quantitatively detected by ELISA. TNF-alpha mRNA from liver macrophages was measured by real time PCR. RESULTS: Irradiation had no influence on cell viability. Apoptosis of irradiated hepatocytes was detected 24h after replacing 50% of medium with supernatants of irradiated liver macrophages 6 h after irradiation (32.0+/-5.8% compared to solely irradiated cells (12+/-2.9%, P=0.02)). In supernatants of hepatocytes, no TNF-alpha secretion could be measured. A radiation dependent increase was found in supernatants of liver macrophages. Addition of anti-TNF-alpha-antibodies to the supernatants of irradiated liver macrophages reduced apoptosis (20+/-0.9%). Incubation of irradiated hepatocytes with purified recombinant TNF-alpha increased apoptosis in irradiated hepatocytes. This effect could be abrogated by additional administration of TNF-alpha-antibodies. CONCLUSIONS: Irradiation leads to susceptibility of hepatocytes to TNF-alpha mediated apoptosis. Liver macrophages may be one of the sources of TNF-alpha in case of liver-irradiation. This cell-cell-interaction may be an important initial step towards RILD and liver fibrosis. |
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Authors:
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Hans Christiansen; Bernhard Saile; Katrin Neubauer-Saile; Stephan Tippelt; Margret Rave-Fränk; Robert Michael Hermann; Josef Dudas; Clemens Friedrich Hess; Heinz Schmidberger; Giuliano Ramadori |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Volume: 72 ISSN: 0167-8140 ISO Abbreviation: Radiother Oncol Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-09-28 Completed Date: 2005-02-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8407192 Medline TA: Radiother Oncol Country: Ireland |
Other Details:
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Languages: eng Pagination: 291-6 Citation Subset: IM |
Affiliation:
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Department of Radiation Oncology, University of Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Cell Survival Hepatocytes / radiation effects* Liver / cytology Macrophages / radiation effects Rats Rats, Wistar Tumor Necrosis Factor-alpha / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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