Protective effect of NSA on intestinal epithelial cells in a necroptosis model
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Wei Dong1,*, Min Zhang2,*, Yaxi Zhu3, Yuanhan Chen1, Xingchen Zhao1, Ruizhao Li1, Li Zhang1, Zhiming Ye1 and Xingling Liang1
1Division of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
2Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
3Department of Pathology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
*These authors have contributed equally to this work
Xingling Liang, email: [email protected]
Keywords: intestinal epithelial cells, inflammatory bowel disease, colitis, necroptosis, necrosulfonamide
Received: June 12, 2017 Accepted: September 05, 2017 Published: September 30, 2017
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-α 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-α 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-α and Z-VAD-fmk.
Conclusion: NSA can inhibit necroptosis in intestinal epithelial cells in vitro and might confer a potential protective effect against IBD.
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