USP15 alleviates the cerulein-induced cell apoptosis and inflammatory injury to AR42J cells through regulating TAB2/3/NF-κB pathway in acute pancreatitis

Acute pancreatitis, characterized by parenchymal cell death and inflammatory process of pancreas, is a lethal disease. USP15 (ubiquitin-specific peptidase 15) belongs to USP family and participates in the ubiquitination system. USP15 was implicated in inflammatory processes and involved in the tumor progression. However, the roles of USP15 in acute pancreatitis-associated inflammation and apoptosis have not been reported yet. Firstly, in vitro cell model of acute pancreatitis was established through incubation of AR42J with cerulein. Results showed that cerulein induced inflammatory response in AR42J with up-regulation of TNF-α, IL-6 and IL-1β. USP15 was up-regulated in cerulein-induced AR42J. Secondly, siRNA-mediated silence of USP15 reduced levels of TNF-α, IL-6 and IL-1β, and pcDNA-mediated over-expression of USP15 enhanced the levels of TNF-α, IL-6 and IL-1β. Moreover, cell apoptosis of cerulein-induced AR42J was suppressed by silence of USP15 with reduced cleaved caspase-3 and cleaved caspase-9, while promoted by USP15 over-expression. Lastly, silence of USP15 decreased protein expression of p65 phosphorylation and TAB (Transforming growth factor-β activated kinase-1 binding protein) 2/3 in cerulein-induced AR42J, while the protein expression was enhanced by USP15 over-expression. In conclusion, USP15 contributed to cerulein-induced AR42J inflammatory response and cells injury through regulation of TAB2/3/NF-κB pathway in acute pancreatitis.

USP15; Cerulein; Apoptosis; Inflammatory; AR42J; TAB2/3/NF-κB; Acute pancreatitis

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