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

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

Volume: 14

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

Affiliation:

• Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008,China

• Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001,China

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

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.

Cite this article as:

Tang Jing , Tan Xiaoxue , Huang Xiangmi , Zhang Jie , Chen Liang, Li Aiyuan*, Wang Deming *, Dual Targeting of Autophagy and NF-κB Pathway by PPARγ Contributes to the Inhibitory Effect of Demethoxycurcumin on NLRP3 Inflammasome Priming, Current Molecular Pharmacology 2021; 14 (5) . https://dx.doi.org/10.2174/1874467214666210301121020