The role of p53 and Fas in a model of acute murine graft-versus-host disease


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YADA, Shinichiro, Noriaki TAKAMURA, Kyoko INAGAKI-OHARA, Melissa O’LEARY, Christoph WASEM, Thomas BRUNNER, Douglas GREEN, Tesu LIN, Michael PINKOSKI, 2005. The role of p53 and Fas in a model of acute murine graft-versus-host disease. In: Journal of Immunology. 174(3), pp. 1291-1297. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/​jimmunol.174.3.1291

@article{Yada2005model-14281, title={The role of p53 and Fas in a model of acute murine graft-versus-host disease}, year={2005}, doi={10.4049/​jimmunol.174.3.1291}, number={3}, volume={174}, issn={0022-1767}, journal={Journal of Immunology}, pages={1291--1297}, author={Yada, Shinichiro and Takamura, Noriaki and Inagaki-Ohara, Kyoko and O’Leary, Melissa and Wasem, Christoph and Brunner, Thomas and Green, Douglas and Lin, Tesu and Pinkoski, Michael} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <bibo:uri rdf:resource=""/> <dcterms:available rdf:datatype="">2011-10-20T10:01:48Z</dcterms:available> <dc:creator>O’Leary, Melissa</dc:creator> <dc:rights>terms-of-use</dc:rights> <dspace:isPartOfCollection rdf:resource=""/> <dc:contributor>Green, Douglas</dc:contributor> <dcterms:rights rdf:resource=""/> <dc:language>eng</dc:language> <dc:contributor>Brunner, Thomas</dc:contributor> <dc:creator>Lin, Tesu</dc:creator> <dc:creator>Brunner, Thomas</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:contributor>O’Leary, Melissa</dc:contributor> <dcterms:bibliographicCitation>Publ. in: Journal of Immunology ; 174 (2005), 3. - pp. 1291-1297</dcterms:bibliographicCitation> <dc:creator>Wasem, Christoph</dc:creator> <dcterms:issued>2005</dcterms:issued> <dc:creator>Green, Douglas</dc:creator> <dc:contributor>Wasem, Christoph</dc:contributor> <dc:creator>Pinkoski, Michael</dc:creator> <dc:date rdf:datatype="">2011-10-20T10:01:48Z</dc:date> <dc:creator>Inagaki-Ohara, Kyoko</dc:creator> <dc:contributor>Takamura, Noriaki</dc:contributor> <dc:contributor>Lin, Tesu</dc:contributor> <dc:contributor>Pinkoski, Michael</dc:contributor> <dcterms:isPartOf rdf:resource=""/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Inagaki-Ohara, Kyoko</dc:contributor> <dc:creator>Yada, Shinichiro</dc:creator> <dcterms:abstract xml:lang="eng">Graft-vs-host disease (GVHD) is a devastating, frequently fatal pathological condition associated with lesions in specific target organs, including the intestine, liver, lung, and skin, as well as pancytopenia and alopecia. Bone marrow (BM) atrophy is observed in acutely diseased animals, but the underlying mechanisms of hemopoietic stem cell depletion remained to be established. We used an experimental mouse model of acute GVHD in which parental cells were injected into F1 hosts preconditioned by sublethal irradiation. The resulting graft-vs-host response was kinetically consistent, resulting in lethality within 3 wk. We observed disease pathology in the liver and small intestine, and consistent with previous observations, we found BM atrophy to be a factor in the onset of acute disease. The product of the protooncogene, p53, is known to be a key player in many physiological examples of apoptosis. We investigated the role of p53 in the apoptosis of BM cells (BMC) during the development of acute disease and found that at least one copy of the p53 gene is necessary for depletion of BM and subsequent lethality in host animals. BM depletion was preceded by induction of the death receptor, Fas, on the surface of host stem cells, and induction of Fas was coincidental with the sensitization of BMC to Fas-mediated apoptosis. Our data indicate that BM depletion in acute GVHD is mediated by p53-dependent up-regulation of Fas on BMC, which leads to Fas-dependent depletion and subsequent disease.</dcterms:abstract> <dcterms:title>The role of p53 and Fas in a model of acute murine graft-versus-host disease</dcterms:title> <dc:contributor>Yada, Shinichiro</dc:contributor> <dc:creator>Takamura, Noriaki</dc:creator> </rdf:Description> </rdf:RDF>

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