NLRP3 is dispensable for d-galactosamine/lipopolysaccharide-induced acute liver failure

The nucleotide-binding domain and leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome is involved in various acute and chronic liver diseases, however, it is not clear whether NLRP3 contributes to d -Galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced acute liver failure (ALF). This study aims to investigate the role of NLRP3 inflammasome in D-GalN/LPS-induced fatal hepatitis. We found that Nlrp3 −/− and WT mice showed similar mortality against a lethal dose of D-GalN/LPS treatment. Serum ALT and AST levels, as well as liver necrosis area and hepatocyte apoptosis, were not significantly different between Nlrp3 −/− and WT mice at 6 h after D-GalN/LPS injection. Moreover, the numbers of intrahepatic F4/80 + cells and Ly6G + cells were comparable in two genotype mice following D-GalN/LPS treatment. Besides, Nlrp3 −/− mice had reduced IL-1β levels but similar TNF-α, IL-6, and MCP-1 levels compared with WT mice upon D-GalN/LPS administration. Our findings revealed that NLRP3 ablation does not protect mice from D-GalN/LPS-induced fatal hepatitis and has a marginal effect on intrahepatic inflammatory response upon D-GalN/LPS treatment. This suggests that NLRP3 inflammasome does not appear to be a major contributor to D-GalN/LPS-induced ALF. • Nlrp3 −/− and WT mice show comparable mortality and liver damage against D-GalN/LPS treatment. • NLRP3 ablation does not affect the hepatocyte apoptosis induced by D-GalN/LPS. • NLRP3 inflammasome has a limited role in the overall intrahepatic inflammatory response in D-GalN/LPS induced ALF.