- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Extracellular DNA (ecDNA) activates immune cells and is involved in the pathogenesis of diseases associated with inflammation such as sepsis, rheumatoid arthritis or metabolic syndrome. DNA can be cleaved by deoxyribonucleases (DNases), some of which are secreted out of cells. The aim of this experiment was to describe plasma DNase activity in relation to extracellular DNA in adult rats, to analyse potential sex differences and to prove whether they are related to endogenous testosterone. Adult Lewis rats (n=28) of both sexes were included in the experiment. Male rats were gonadectomized or sham-operated and compared to intact female rats. Plasma ecDNA and DNase activity were measured using fluorometry and single radial enzyme diffusion assay, respectively. Concentrations of nuclear ecDNA and mitochondrial ecDNA were determined using real-time PCR. Females had 60% higher plasma DNase activity than males ( p=0.03). Gonadectomy did not affect plasma DNase in males. Neither the concentration of total ecDNA, nor nuclear or mitochondrial DNA in plasma differed between the groups. No significant correlations between DNase and ecDNA were found. From previous studies on mice, it was expected, that male rats will have higher DNase activity. In contrast, our study in rats showed the opposite sex difference. This sex difference seems not to be caused by endogenous testosterone. Interestingly, no sex differences were observed in plasma ecDNA suggesting a complex or missing association between plasma ecDNA and DNase. The observed sex difference in plasma DNase should be taken into account in animal models of ecDNA-associated diseases.
- MeSH
- deoxyribonukleasy krev MeSH
- DNA krev MeSH
- orchiektomie MeSH
- pohlavní dimorfismus * MeSH
- potkani inbrední LEW MeSH
- testosteron krev MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.
- MeSH
- biologické markery metabolismus MeSH
- deoxyribonukleasy metabolismus MeSH
- DNA krev metabolismus MeSH
- endoskopie MeSH
- extracelulární pasti účinky léků metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- kolitida krev chemicky indukované patologie MeSH
- mitochondriální DNA krev MeSH
- myši inbrední C57BL MeSH
- ornithin analogy a deriváty farmakologie MeSH
- peptidylarginindeiminasa typu 4 metabolismus MeSH
- síran dextranu MeSH
- streptonigrin farmakologie MeSH
- střeva účinky léků patologie MeSH
- střevní sliznice účinky léků patologie MeSH
- stupeň závažnosti nemoci MeSH
- zánět krev patologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
The aim of this study was to investigate the potential of extracellular DNA as a prognostic and/or therapeutic target in inflammatory bowel disease. Fifty male C57BL/6J mice were used in the experiment. Acute colitis was induced by intake of 2% dextran sulphate sodium (DSS) for seven days followed by three days of water intake. DNase I was injected intravenously on days 3 and 7. Plasmatic levels of extracellular DNA (ecDNA) were measured on days 6 and 10. Weight loss, stool consistency and liquid intake were monitored throughout the experiment. Colon length and weight, myeloperoxidase activity and tumour necrosis factor α (TNF-α) levels were measured at sacrifice. DSS-treated mice displayed severe colitis, as shown by disease activity parameters. Both groups with colitis (DNase treated and untreated) had significantly poorer weight loss, colon length and stool consistency compared with control groups on water. No differences between the DNasetreated and untreated DSS groups were recorded. Myeloperoxidase activity and levels of TNF-α in colonic tissue were notably greater in both groups with colitis compared to controls. In addition, both biochemical markers were improved in the DNasetreated group with colitis compared to the untreated group. Although the disease activity was proved by several independent parameters in both groups with colitis, levels of ecDNA did not show any difference between the groups throughout or at the end of experiment. The role of ecDNA in experimental colitis has not been confirmed. However, DNase I injection resulted in some improvement, and thus should be studied in more detail.
- MeSH
- biologické markery metabolismus MeSH
- cílená molekulární terapie * MeSH
- deoxyribonukleasa I terapeutické užití MeSH
- DNA metabolismus MeSH
- kolitida farmakoterapie patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- prognóza MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neutrophils play an important role as the central mediators of the innate immune defence response, providing the first line of host protection. It was shown that these cells can trap and kill various microorganisms through different ways. One of them is a release of neutrophil extracellular traps (NETs) composed of chromatin fibrils and antimicrobial proteins. There is the evidence that the release of NETs does not have only a beneficial effect. NETs can trap and kill microorganisms and pathogens, however on the other hand the same pathway can also cause the damage of the organism by various mechanisms. NETs participate in the pathogenesis of a lot of inflammatory and autoimmune disorders, such as thrombosis, atherosclerosis, cystic fibrosis, periodontitis, lupus, rheumatoid arthritis and others. The aim of this review is to summarize information about the release of NETs and their beneficial, but also detrimental effect during various diseases. The better characterization and understanding of the dual role of NETosis during these diseases is necessary for the early diagnosis and more effective treatment.
- MeSH
- apoptóza MeSH
- autoimunitní nemoci imunologie metabolismus patologie MeSH
- cystická fibróza imunologie metabolismus patologie MeSH
- extracelulární pasti imunologie metabolismus mikrobiologie MeSH
- kardiovaskulární nemoci imunologie metabolismus patologie MeSH
- neutrofily metabolismus patologie MeSH
- parodontitida imunologie metabolismus patologie MeSH
- zánět imunologie patofyziologie patologie MeSH
Clinical observations and animal experiments have shown that higher fetal DNA in maternal plasma could participate on the pathogenesis of preeclampsia. The understudied factor that could participate in interindividual variability in cell-free DNA is enzymatic activity of deoxyribonuclease (DNase). We have found that healthy pregnant animals have higher plasma DNase activity than healthy pregnant women. Injection of cell-free fetal DNA into pregnant animals had no effect on DNase activity. Interspecies differences in DNase activity should be considered in animal experiments focusing on the role of fetal DNA in preeclampsia and cell-free DNA in other disease models.
- MeSH
- biologické markery krev MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- plod metabolismus MeSH
- potkani Wistar MeSH
- preeklampsie krev MeSH
- těhotenství krev MeSH
- volné cirkulující nukleové kyseliny krev MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství krev MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
