Document Detail


Interferon-induced TRAIL-independent cell death in DNase II-/- embryos.
MedLine Citation:
PMID:  20706988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The chromosomal DNA of apoptotic cells and the nuclear DNA expelled from erythroid precursors is cleaved by DNase II in lysosomes after the cells or nuclei are engulfed by macrophages. DNase II(-/-) embryos suffer from lethal anemia due to IFN-beta produced in the macrophages carrying undigested DNA. Here, we show that Type I IFN induced a caspase-dependent cell death in human epithelial cells that were transformed to express a high level of IFN type I receptor. During this death process, a set of genes was strongly activated, one of which encoded TRAIL, a death ligand. A high level of TRAIL mRNA was also found in the fetal liver of the lethally anemic DNase II(-/-) embryos, and a lack of IFN type I receptor in the DNase II(-/-) IFN-IR(-/-) embryos blocked the expression of TRAIL mRNA. However, a null mutation in TRAIL did not rescue the lethal anemia of the DNase II(-/-) embryos, indicating that TRAIL is dispensable for inducing the apoptosis of erythroid cells in DNase II(-/-) embryos, and therefore, that there is a TRAIL-independent mechanism for the IFN-induced apoptosis.
Authors:
Yusuke Kitahara; Kohki Kawane; Shigekazu Nagata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2590-8     Citation Subset:  IM    
Affiliation:
Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Kyoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspases / metabolism
Cell Death / genetics,  immunology
Cell Line
Embryo Loss / genetics,  immunology
Endodeoxyribonucleases / genetics
Epithelial Cells / immunology,  metabolism*,  pathology
Humans
Interferon Type I / immunology,  metabolism
Liver / immunology,  metabolism*,  pathology
Mice
Mice, Knockout
Receptors, Interferon / genetics,  immunology,  metabolism*
Sequence Deletion / genetics
TNF-Related Apoptosis-Inducing Ligand / genetics,  immunology,  metabolism*
Transgenes / genetics
Chemical
Reg. No./Substance:
0/Interferon Type I; 0/Receptors, Interferon; 0/TNF-Related Apoptosis-Inducing Ligand; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.22.1/deoxyribonuclease II; EC 3.4.22.-/Caspases

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