The NLRP3 inflammasome has been implicated in the pathogenesis of wide variety of human diseases. Recently, non-canonical inflammasome activation emerges as an interesting novel inflammasome which is caspase-11 dependent. Inappropriate inflammation can lead to persistent infection of pathogens, while excessive inflammation can cause chronic or systemic inflammatory diseases.
In this study, the inhibitory effect of C1 compound was explored on NLRP3 inflammasome activation in LPS-primed bone marrow-derived macrophages (BMDMs). C1 suppressed the cleavage of IL-1β, Caspase-1, and pyroptotic cell death in a dose-dependent manner through the attenuation of NLRP3 and noncanonical inflammasome activation. In addition, C1 inhibited the formation of cytosolic macromolecular ASC as dimer or oligomer. C1 treatment also suppressed the translocation of NLRP3 and ASC from the Triton X-100 soluble fraction to insoluble fraction. Furthermore, C1 showed protective action on LPS-induced lethality. Thus, our results provide a small compound C1 inhibitor for NLRP3 and indicate that NLRP3 can be targeted in vivo to combat NLRP3-diriven diseases.