Isoliquiritigenin and glycyrrhizin inhibit the inflammasome activation in a different manner. (P1246)

Abstract A soponin glycyrrhizin (GL) and a chalcone isoliquiritigenin(ILG) are representative components of Glycyrrhiza uralensis, which attenuate inflammatory responses mediated by TLR4. We have showed that GL and ILG suppressed different steps of the LPS sensor TLR4/MD-2 complex signaling at the receptor level. GL and ILG attenuated LPS binding to the TLR4/MD-2 complex and LPS-induced TLR4 homodimerization, respectively. In the present study, we examined effects of ILG and GL on IL-1β production in macrophage. When bone marrow-derived macrophages were stimulated with LPS to prime TLR4 signaling pathway followed by ATP to activate NLRP3 inflammasome, significant IL-1β production was observed. However, addition of ILG or GL together with ATP severely impaired the IL-1β production without changing the pro-IL-1β expression levels. We infer from these results that ILG and GL inhibit the NLRP3 inflammasome activation in both priming phase as well as activating phase. We also investigated effects of ILG and GL on the AIM2 inflammasome activation and found that GL but not ILG could suppress its activation, while both ILG and GL could suppress ATP-dependent inflammasome activation.We will discuss molecular mechanisms by which these compounds suppress inflammasome activation.