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
Diabetes is associated with dire peripheral sequelae including foot ulcers and amputations. A recent article by Wong et al. demystifies this connection by demonstrating that the neutrophil defense mechanism of extruding decondensed chromatin, termed NETosis, mediates delayed wound healing in diabetes and provides a therapeutic strategy for this indication.
- MeSH
- citrulin metabolismus MeSH
- extracelulární pasti * účinky léků MeSH
- hojení ran * účinky léků MeSH
- hydrolasy genetika metabolismus MeSH
- komplikace diabetu patologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
