• Home
  • Search Results
  • Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis.

Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis.

Biomedicines (2020-08-09)
Elliot Yi-Hsin Lin, Hsuan-Ju Lai, Yuan-Kai Cheng, Kai-Quan Leong, Li-Chieh Cheng, Yi-Chun Chou, Yu-Chun Peng, Yi-Hsuan Hsu, Hao-Sen Chiang
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Picrylsulfonic acid solution, 5 % (w/v) in H2O, BioReagent, suitable for determination of primary amines
Sigma-Aldrich
Citrate-dextrose solution (ACD), sterile-filtered
Sigma-Aldrich
1-Bromo-3-chloropropane, for isolation of RNA