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.

• Keywords
• PAD4, cell-free DNA, deoxyribonuclease activity, neutrophil extracellular traps, ulcerative colitis,
• MeSH
• Biomarkers metabolism   MeSH
• Deoxyribonucleases metabolism   MeSH
• DNA blood   metabolism   MeSH
• Endoscopy MeSH
• Extracellular Traps drug effects   metabolism   MeSH
• Extracellular Space metabolism   MeSH
• Colitis blood   chemically induced   pathology   MeSH
• DNA, Mitochondrial blood   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Ornithine analogs & derivatives   pharmacology   MeSH
• Protein-Arginine Deiminase Type 4 metabolism   MeSH
• Dextran Sulfate MeSH
• Streptonigrin pharmacology   MeSH
• Intestines drug effects   pathology   MeSH
• Intestinal Mucosa drug effects   pathology   MeSH
• Severity of Illness Index MeSH
• Inflammation blood   pathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Deoxyribonucleases MeSH
• DNA MeSH
• DNA, Mitochondrial MeSH
• N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide MeSH Browser
• Ornithine MeSH
• Protein-Arginine Deiminase Type 4 MeSH
• peptidylarginine deiminase 4, mouse MeSH Browser
• Dextran Sulfate MeSH
• Streptonigrin MeSH