title: Interferon-induced TRAIL-independent cell death in DNase II-/- embryos.
abstract: 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: Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Yoshida-Konoe, Kyoto, Japan.
authors: Yusuke
authors: Y
authors: Kitahara
authors: Kohki
authors: K
authors: Kawane
authors: Shigekazu
authors: S
authors: Nagata
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D020964:Embryo Loss / Q000235:genetics / Q000276:immunology; D004706:Endodeoxyribonucleases / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D007370:Interferon Type I; D017471:Receptors, Interferon; D053221:TNF-Related Apoptosis-Inducing Ligand; D004706:Endodeoxyribonucleases; C019329:deoxyribonuclease II; D020169:Caspases