Effect of free fatty acid on NALP3 inflammasome signaling pathway in THP-1 macrophages / 中南大学学报(医学版)

ABSTRACT

OBJECTIVE@#To investigate the potential effect of NALP3 inflammasome on the occurrence and development of nonalcoholic steatohepatitis (NASH).@*METHODS@#THP-1 macrophages were cultured for 24 h by palmitic acid at various concentrations. The THP-1 macrophages were pretreated with N-acetyl-cysteine at different doses for 24 h before the palmitic acid cultivation. ROS production was determined by flow cytometry. The expression of IL- 1β was detected by ELISA; the expressions of NALP3 protein and caspase-1 protein were detected by immunofluorescence; NALP3, ASC, and caspase-1 mRNA were measured by real-time PCR.@*RESULTS@#Compared with the THP-1 macrophages without palmitic acid, the level of ROS, NALP3 protein and caspase-1 protein, and the expression of IL-1β were increased after palmitic acid treatment in a dose dependent manner (P<0.05). Compared with the THP-1 macrophages with palmitic acid (400 μmol/L), the level of NALP3 mRNA (P<0.05), the level of NALP3 protein and caspase-1 protein (P<0.05), the expression of IL-1β (P<0.05) were decreased after preadministration of N-acetyl-cysteine in a dose dependent manner.@*CONCLUSION@#ROS induced by free fatty acid can regulate the activation of NALP3 inflammasome signaling pathway leading to the release of inflammatory cytokines. This pathway may be the possible mechanism of NASH.