The NLRP3 inflammasome mediates liver failure by activating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling.

Abstract

ObjectivesIn this prospective case–control study, we explored the regulatory roles of the NLRP3 inflammasome in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF).MethodsThirty patients with HBV-ACLF, 30 patients with chronic hepatitis B, and 30 healthy individuals were enrolled. Real-time reverse transcription polymerase chain reaction was used to assess mRNA levels in peripheral blood mononuclear cells and serum protein levels were assessed by enzyme-linked immunosorbent assay.ResultsSerum levels of alanine aminotransferase, asparagine aminotransferase, total bilirubin, and direct bilirubin in patients with HBV-ACLF were increased. Transcript levels of NLRP3 and ASC and protein levels of interleukin (IL)-1β, IL-18, and sCD40L were elevated in patients with HBV-ACLF. Expression of the NLRP3 inflammasome signaling pathway components procaspase-1 and pro-IL-1β was elevated in patients with HBV-ACLF.ConclusionsThis prospective case-control study demonstrated that significant activation of the NLRP3 inflammasome occurs in patients with HBV-ACLF. The activated NLRP3 inflammasome mediated liver failure by stimulating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling.