Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis
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 demonstrate...
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MDPI AG
2020-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/8/275 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elliot Yi-Hsin Lin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:56:23Z |
| format | Article |
| id | doaj.art-d1dfb23cc69b44f299b72097fedcb0db |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T17:56:23Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d1dfb23cc69b44f299b72097fedcb0db2023-11-20T09:11:01ZengMDPI AGBiomedicines2227-90592020-08-018827510.3390/biomedicines8080275Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental ColitisElliot Yi-Hsin Lin0Hsuan-Ju Lai1Yuan-Kai Cheng2Kai-Quan Leong3Li-Chieh Cheng4Yi-Chun Chou5Yu-Chun Peng6Yi-Hsuan Hsu7Hao-Sen Chiang8Department of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanGenome and Systems Biology Degree Program, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Life Science, National Taiwan University, Taipei 10617, TaiwanAberrant 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.https://www.mdpi.com/2227-9059/8/8/275neutrophil extracellular traps (NETs)intestinal barrier integrityDNase IDSS/TNBS-induced colitis |
| spellingShingle | 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 Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis Biomedicines neutrophil extracellular traps (NETs) intestinal barrier integrity DNase I DSS/TNBS-induced colitis |
| title | Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis |
| title_full | Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis |
| title_fullStr | Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis |
| title_full_unstemmed | Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis |
| title_short | Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis |
| title_sort | neutrophil extracellular traps impair intestinal barrier function during experimental colitis |
| topic | neutrophil extracellular traps (NETs) intestinal barrier integrity DNase I DSS/TNBS-induced colitis |
| url | https://www.mdpi.com/2227-9059/8/8/275 |
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