691 Cell-Specific Roles of miR-155 and miR-122 in Inflammation, Immunity and Fibrosis in Non-Alcoholic Steatohepatitis

Abstract

ligand. IL-1β and inflammasome components were measured from the cells and supernatant. TLR2 deficient mice were fed a CDAA diet to assess the requirement of TLR2 in NASH. (Results) The CDAA diet feeding for 22 weeks induced steatohepatitis, obesity and insulin resistance. Hepatic and blood FFAs were increased in WT mice fed the CDAA diet compared with those fed a standard diet. Hepatic and blood IL-1β levels were also increased in WT mice fed the CDAA diet. CDAA diet feeding increased in expression of inflammasome components including nalp3, nalp1, ASC, caspase-1, and AIM2. InWTKupffer cells, palmitic acid did not increase expression of IL-1β and inflammasome components. In contrast, a synthetic TLR2 ligand increased gene expression of IL-1β as well as an inflammasome component nalp3. Although a synthetic TLR2 ligand increased mRNA expressions of IL-1β and nalp3, active form of IL-1β was not detected from the supernatant. Interestingly, palmitic acids treatment induced secretion of active IL-1β form in Kupffer cells primed with TLR2 ligand. Finally, we tested the role of TLR2 in murine NASH model. TLR2 deficient mice fed the CDAA showed less steatohepatitis and lower expression of inflammasome components than WT mice. (Conclusion) TLR2 signaling induces expression of inflammasome components and the subsequent treatment with palmitic acid induces activation of IL-1β. Thus, activation of inflammasome and IL-1β require both FFA stimulation and TLR2 signaling in NASH.