Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice.
Animals
Biomarkers
/ metabolism
Colitis
/ blood
DNA
/ blood
DNA, Mitochondrial
/ blood
Deoxyribonucleases
/ metabolism
Dextran Sulfate
Endoscopy
Extracellular Space
/ metabolism
Extracellular Traps
/ drug effects
Inflammation
/ blood
Intestinal Mucosa
/ drug effects
Intestines
/ drug effects
Mice, Inbred C57BL
Ornithine
/ analogs & derivatives
Protein-Arginine Deiminase Type 4
/ metabolism
Severity of Illness Index
Streptonigrin
/ pharmacology
PAD4
cell-free DNA
deoxyribonuclease activity
neutrophil extracellular traps
ulcerative colitis
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
06 01 2021
06 01 2021
Historique:
received:
11
11
2020
revised:
25
12
2020
accepted:
31
12
2020
entrez:
9
1
2021
pubmed:
10
1
2021
medline:
25
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33418977
pii: cells10010081
doi: 10.3390/cells10010081
pmc: PMC7825321
pii:
doi:
Substances chimiques
Biomarkers
0
DNA, Mitochondrial
0
N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide
0
Streptonigrin
261Q3JB310
DNA
9007-49-2
Dextran Sulfate
9042-14-2
Ornithine
E524N2IXA3
Deoxyribonucleases
EC 3.1.-
Protein-Arginine Deiminase Type 4
EC 3.5.3.15
peptidylarginine deiminase 4, mouse
EC 3.5.3.15
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Am J Physiol Gastrointest Liver Physiol. 2017 May 1;312(5):G457-G463
pubmed: 28209603
Biomed Pharmacother. 2017 Sep;93:8-16
pubmed: 28622595
Sci Adv. 2020 May 29;6(22):eaax8847
pubmed: 32523980
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Inflamm Regen. 2020 Jul 21;40:18
pubmed: 32714475
Adv Exp Med Biol. 2020;1263:13-23
pubmed: 32588320
Obstet Gynecol. 2000 Dec;96(6):991-6
pubmed: 11084191
Int J Mol Sci. 2019 Jul 26;20(15):
pubmed: 31357438
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Clin Chem. 2003 Mar;49(3):495-6
pubmed: 12600963
Clin Rev Allergy Immunol. 2021 Oct;61(2):194-211
pubmed: 32740860
Lancet. 2018 Dec 23;390(10114):2769-2778
pubmed: 29050646
Cancer Res. 2019 Apr 1;79(7):1274-1284
pubmed: 30894374
J Investig Med. 2020 Jun;68(5):992-1001
pubmed: 32393477
Acc Chem Res. 2019 Mar 19;52(3):818-832
pubmed: 30844238
PLoS One. 2012;7(12):e52249
pubmed: 23284954
Biomedicines. 2020 Aug 05;8(8):
pubmed: 32764411
Folia Biol (Praha). 2018;64(1):10-15
pubmed: 29871733
Int Immunopharmacol. 2020 Jul;84:106583
pubmed: 32416455
J Surg Res. 2017 Apr;210:231-243
pubmed: 28457334
PLoS One. 2018 Aug 13;13(8):e0197649
pubmed: 30102706
Annu Rev Immunol. 2002;20:709-60
pubmed: 11861616
Anticancer Res. 2007 May-Jun;27(3A):1257-65
pubmed: 17593617
Comp Immunol Microbiol Infect Dis. 2017 Jun;52:48-57
pubmed: 28673462
Oncogene. 2010 May 27;29(21):3153-62
pubmed: 20190809
Folia Biol (Praha). 2018;64(5-6):167-172
pubmed: 30938673
Sci Adv. 2016 Mar 25;2(3):e1501332
pubmed: 27051864
Adv Clin Exp Med. 2019 May;28(5):587-592
pubmed: 30085433
Clin Lab. 2016 Dec 1;62(12):2395-2404
pubmed: 28164563
J Crohns Colitis. 2019 May 27;13(6):772-784
pubmed: 30715224
Science. 2004 Mar 5;303(5663):1532-5
pubmed: 15001782
Mitochondrion. 2016 Jul;29:59-64
pubmed: 27181048
Expert Rev Gastroenterol Hepatol. 2019 Jun;13(6):591-602
pubmed: 30101634
Pediatr Surg Int. 2014 Dec;30(12):1199-206
pubmed: 25367095
J Cancer. 2020 May 18;11(15):4384-4396
pubmed: 32489457
Semin Thromb Hemost. 2020 Sep;46(6):724-734
pubmed: 32906176
J Vis Exp. 2012 Feb 01;(60):
pubmed: 22331082
JCI Insight. 2020 Jul 9;5(13):
pubmed: 32484790
Genome Biol. 2019 Nov 28;20(1):257
pubmed: 31779668
PLoS Pathog. 2011 Apr;7(4):e1001310
pubmed: 21533068
Blood Purif. 2016;41(1-3):34-40
pubmed: 26960212
Int J Environ Res Public Health. 2018 Aug 07;15(8):
pubmed: 30087270
Am J Physiol Gastrointest Liver Physiol. 2011 Jun;300(6):G929-38
pubmed: 21415415
PLoS One. 2014 Jun 23;9(6):e100514
pubmed: 24955978
Pathol Oncol Res. 2014 Oct;20(4):867-77
pubmed: 24723054
Autoimmune Dis. 2011;2011:945861
pubmed: 21687600