Effect Of NALP3Inflammasome Signaling Pathway In THP-1Macrophages Induced By Free Fatty Acid

Objective:The study was designed to investigate the potential effects of NALP3inflammasome on the occurrence and development of nonalcoholic steatohepatitis.Methods:THP-1macrophages were cultured for24h by palmitic acid with various concentrations (50μmol/L、100μmol/L、200μmol/L、400μmol/L).Pretreatment of the THP-1macrophages with N-acetyl-cysteine at different doses before palmitic acid (400μmol/L) cultivation for24h.ROS production determined by flow cytometry and fluorescence microscope, The expression of IL-1β were detected by ELISA,The expressions of NALP3protein and caspase-1protein was detected by immunofluorescence,NALP3、ASC、caspase-1mRNA was measured by Real-time PCR.Results:Compared to the THP-1macrophages without palmitic acid, the level of ROs、NALP3protein and caspase-1protein, the expression of IL-1β were increased after treatment by palmitic acid in a dose-dependent fashion(P<0.05). Compared to the THP-1macrophages with palmitic acid (400μmol/L), the level of NALP3mRNA(P<0.05), the level of T NALP3protein and caspase-1protein(P<0.01), the expression of IL-1β(P<0.05) were decreased after preadministration by N-acetyl-cysteine in a dose-dependent fashion.Conclusions:ROS induced by Free fatty acid can regulate the activation of NALP3Inflammasome signaling pathway leading to the release of inflammatory cytokines,This pathway may be the possible mechanism of NASH.