Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxyribonuclease (DNase) II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. DNase II-deficient mouse embryos accumulate undigested DNA in macrophages, and die in feto because of the activation of the interferon beta (IFNbeta) gene. Here, we found that the F4/80-positive macrophages in DNase II(-/-) fetal liver specifically produce a set of cytokines such as IFNbeta, TNFalpha, and CXCL10. Whereas, IFN-inducible genes (2'5'-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in macrophages but also in other F4/80-negative cells. When DNase II(-/-) macrophages or embryonal fibroblasts engulfed apoptotic cells, they expressed the IFNbeta and CXCL10 genes. The ablation of Toll-like receptor (TLR) 3 and 9, or their adaptor molecules (MyD88 and TRIF), had no effect on the lethality of the DNase II(-/-) mice. These results indicate that there is a TLR-independent sensing mechanism to activate the innate immunity for the endogenous DNA escaping lysosomal degradation.
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PMID:Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. 1630 43

DNase II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. Macrophages in DNase II-deficient mice accumulate undigested DNA and constitutively produce IFN-beta as well as TNF-alpha. The IFN-beta causes severe anemia in the DNase II(-/-) embryos, which die prenatally. On the other hand, when the DNase II gene is inactivated postnatally, mice develop polyarthritis owing to the TNF-alpha produced by macrophages. Here, we showed that the IFN-beta gene activation in DNase II(-/-) mice is dependent on IFN regulatory factor (IRF) 3 and 7. Accordingly, DNase II(-/-)IRF3(-/-)IRF7(-/-) mice do not suffer from anemia, but they still produce TNF-alpha, and age-dependently develop chronic polyarthritis. A microarray analysis of the gene expression in the fetal liver revealed a set of genes that is induced in DNase II(-/-) mice in an IRF3/IRF7-dependent manner, and another set that is induced independent of these factors. These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners.
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PMID:IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation. 1899 Dec 90

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.
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PMID:Interferon-induced TRAIL-independent cell death in DNase II-/- embryos. 2070 88