Dual Targeting of Autophagy and NF-κB Pathway by PPARγ Contributes to the Inhibitory Effect of Demethoxycurcumin on NLRP3 Inflammasome Priming

(E-pub Ahead of Print)

Author(s): Jing Tang, Xiaoxue Tan, Xiangmi Huang, Jie Zhang, Liang Chen, Aiyuan Li*, Deming Wang*

Journal Name: Current Molecular Pharmacology


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Abstract:

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-1β expression. Meanwhile, DMC diminished NLRP3-dependent IL-1β maturation, caspase-1 activation, IL-1β, 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-κB. Additionally, DMC significantly increased the PPARγ expression, and the effects of DMC in NF- κB inhibition, autophagy, and NLRP3 inflammasome priming were abrogated by specific PPARγ antagonist T0070907.

Conclusion: The evidence presented here has confirmed that DMC increases PPARγ expression, resulting in autophagy and NF-κB inhibition, and subsequently inhibits LPS-induced NLRP3 inflammasome priming and subsequent activation.

Keywords: Demethoxycurcumin, NLRP3, PPARγ, NF-κB, autophagy.

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Article Details

Published on: 01 March, 2021
(E-pub Ahead of Print)
DOI: 10.2174/1874467214666210301121020

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