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Open AccessArticle

Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis

1
Department of Life Science, National Taiwan University, Taipei 10617, Taiwan
2
Genome and Systems Biology Degree Program, National Taiwan University, Taipei 10617, Taiwan
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(8), 275; https://doi.org/10.3390/biomedicines8080275
Received: 2 July 2020 / Revised: 21 July 2020 / Accepted: 30 July 2020 / Published: 5 August 2020
Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis. View Full-Text
Keywords: neutrophil extracellular traps (NETs); intestinal barrier integrity; DNase I; DSS/TNBS-induced colitis neutrophil extracellular traps (NETs); intestinal barrier integrity; DNase I; DSS/TNBS-induced colitis
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Lin, E. .-H.; Lai, H.-J.; Cheng, Y.-K.; Leong, K.-Q.; Cheng, L.-C.; Chou, Y.-C.; Peng, Y.-C.; Hsu, Y.-H.; Chiang, H.-S. Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis. Biomedicines 2020, 8, 275.

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