Cargando…
Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice
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 inflammator...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825321/ https://www.ncbi.nlm.nih.gov/pubmed/33418977 http://dx.doi.org/10.3390/cells10010081 |
_version_ | 1783640280397774848 |
---|---|
author | Maronek, Martin Gromova, Barbora Liptak, Robert Konecna, Barbora Pastorek, Michal Cechova, Barbora Harsanyova, Maria Budis, Jaroslav Smolak, David Radvanszky, Jan Szemes, Tomas Harsanyiova, Jana Kralova Trancikova, Alzbeta Gardlik, Roman |
author_facet | Maronek, Martin Gromova, Barbora Liptak, Robert Konecna, Barbora Pastorek, Michal Cechova, Barbora Harsanyova, Maria Budis, Jaroslav Smolak, David Radvanszky, Jan Szemes, Tomas Harsanyiova, Jana Kralova Trancikova, Alzbeta Gardlik, Roman |
author_sort | Maronek, Martin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7825321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78253212021-01-24 Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice Maronek, Martin Gromova, Barbora Liptak, Robert Konecna, Barbora Pastorek, Michal Cechova, Barbora Harsanyova, Maria Budis, Jaroslav Smolak, David Radvanszky, Jan Szemes, Tomas Harsanyiova, Jana Kralova Trancikova, Alzbeta Gardlik, Roman Cells Article 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. MDPI 2021-01-06 /pmc/articles/PMC7825321/ /pubmed/33418977 http://dx.doi.org/10.3390/cells10010081 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maronek, Martin Gromova, Barbora Liptak, Robert Konecna, Barbora Pastorek, Michal Cechova, Barbora Harsanyova, Maria Budis, Jaroslav Smolak, David Radvanszky, Jan Szemes, Tomas Harsanyiova, Jana Kralova Trancikova, Alzbeta Gardlik, Roman Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title | Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title_full | Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title_fullStr | Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title_full_unstemmed | Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title_short | Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice |
title_sort | extracellular dna correlates with intestinal inflammation in chemically induced colitis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825321/ https://www.ncbi.nlm.nih.gov/pubmed/33418977 http://dx.doi.org/10.3390/cells10010081 |
work_keys_str_mv | AT maronekmartin extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT gromovabarbora extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT liptakrobert extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT konecnabarbora extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT pastorekmichal extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT cechovabarbora extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT harsanyovamaria extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT budisjaroslav extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT smolakdavid extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT radvanszkyjan extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT szemestomas extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT harsanyiovajana extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT kralovatrancikovaalzbeta extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice AT gardlikroman extracellulardnacorrelateswithintestinalinflammationinchemicallyinducedcolitisinmice |