Protective effect and mechanism of MCC950 on lipopolysaccharide induced pancreatic acinar cell inflammation
Objective To explore the effect and related mechanism of MCC950,an inflammasome inhibitor of NLRP-3,on blocking lipopolysaccharide induced inflammation and pyroptosis in pancreatic acinar cells (PACs).Methods Mouse pancreatic acinar cells (MPACs)were subcultured and divided into four groups:blank control group (Control group ),lipopolysaccharide (LPS ) group,LPS+MCC950 intervention group (MCC950 group),and antioxidant N-acetylcysteine (NAC group).The cells were cultured for 48 h.Real time reverse transcription polymerase chain reaction (RT-PCR)and western blot (WB)experiments were performed to detect and analyze the mRNA and protein expression levels of the NLRP-3 signaling pathway NLRP-3,ASC,caspase-1,IL-1β,and IL-18 and the cell apoptosis pathway caspase-11,and GSDMD.Enzyme linked immu-nosorbent assay (ELISA)was used to detect the level of malondialdehyde (MDA),a reactive oxygen species in-dex.Cell apoptosis was detected by Hoechst33342 staining.Results MCC950 and NAC antioxidant intervention effectively inhibited LPS induced apoptosis of MPACs.Compared with the control group,the addition of LPS sig-nificantly increased the level of MDA in MPACs cells,while the intervention of MCC950 and antioxidant NAC ef-fectively inhibited LPS induced high expression of MDA in MPACs (P<0.01 ).The intervention of MCC950 and antioxidant NAC effectively inhibited the high expression of mRNA and protein NLRP-3,ASC,caspase-1,IL-1 β,IL-18,caspase-11,and GSDMD in LPS induced MPACs cells (P<0.01).Conclusion MCC950 has a protective effect on LPS induced acute pancreatitis,which may be related to the inhibition of expression of mRNA and protein related to the cell apoptosis,and NLRP-3 signaling pathway.
pancreatic acinar cellsNOD-like receptor protein 3lipopolysaccharideMCC950pyroptosis
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