Dual Targeting of Autophagy and NF-kappa B Pathway by PPAR gamma Contributes to the Inhibitory Effect of Demethoxycurcumin on NLRP3 Inflammasome Priming

Background: Demethoxycurcumin (DMC), a natural derivative of curcumin, has anti-inflammatory activities. However, the mechanism has not been fully elucidated. Objective: The aim of the current study was to investigate the role of DMC on NLRP3 inflammasome priming. Methods: Protein expression was quantified by western blotting. Inflammatory cytokines were measured by ELISA. Autophagosomes were evaluated by transmission electron microscopy. Results: DMC inhibited LPS-stimulated NLRP3, pro-caspase-1, and pro-IL-1 beta expression. Meanwhile, DMC diminished NLRP3-dependent IL-1 beta maturation, caspase-1 activation, IL-1 beta, and IL-18 production caused by LPS plus ATP. Moreover, DMC induced autophagy and autophagy inhibitor 3-MA abrogated the role of DMC on NLRP3 inflammasome priming and subsequent activation. DMC also inhibited LPS-stimulated phosphorylation and nuclear translocation of p65 NF-kappa B. Additionally, DMC significantly increased the PPAR gamma expression, and the effects of DMC in NF-kappa B inhibition, autophagy, and NLRP3 inflammasome priming were abrogated by specific PPAR gamma antagonist T0070907. Conclusion: The evidence presented here has confirmed that DMC increases PPAR gamma expression, resulting in autophagy and NF-kappa B inhibition, and subsequently inhibits LPS-induced NLRP3 inflammasome priming and subsequent activation.