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Protective effect of NSA on intestinal epithelial cells in a necroptosis model

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 i...

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Detalles Bibliográficos
Autores principales: Dong, Wei, Zhang, Min, Zhu, Yaxi, Chen, Yuanhan, Zhao, Xingchen, Li, Ruizhao, Zhang, Li, Ye, Zhiming, Liang, Xingling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689721/
https://www.ncbi.nlm.nih.gov/pubmed/29156831
http://dx.doi.org/10.18632/oncotarget.21418
Descripción
Sumario: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.