Journal
ONCOTARGET
Volume 8, Issue 49, Pages 86726-86735Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21418
Keywords
intestinal epithelial cells; inflammatory bowel disease; colitis; necroptosis; necrosulfonamide
Categories
Funding
- National Natural Science Foundation of China [81570609, 81600412]
- Guangdong Natural Science Foundation [2016A030313767]
- Guangdong Medical Research Foundation [A2014264]
Ask authors/readers for more resources
Objective: This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF-alpha and Z-VAD-fmk, and the cells were treated with or without NSA. Morphologic changes, manner of cell death and the levels of phosphorylation of receptor-interacting protein kinase 3 (p-RIPK3) and mixed-lineage kinase domain-like (p-MLKL) were detected. Results: In the TNBS-induced colitis in mice, TUNEL-positive and caspase-3-negative cells were observed in the intestinal mucosa, and p-RIPK3 was found to be elevated. Under the stimulation of TNF-a and Z-VAD-fmk, the morphologic damage in the Caco-2 cells was aggravated, the proportion of necrosis was increased, and the level of p-RIPK3 and p-MLKL were increased, confirming that the regulated cell death was necroptosis. NSA reversed the morphological abnormalities and reduced necrotic cell death induced by TNF-a and Z-VAD-fmk. Conclusion: NSA can inhibit necroptosis in intestinal epithelial cells in vitro and might confer a potential protective effect against IBD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available