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

Author(s):

Jing Tang, Xiaoxue Tan, Xiangmi Huang, Jie Zhang, Liang Chen, Aiyuan Li* and Deming Wang*   Pages 1 - 8 ( 8 )

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.

Affiliation:

Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, changsha, Hunan, 410008, Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001, Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, changsha, Hunan, 410008, Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, changsha, Hunan, 410008, Department of Anesthesiology, Hunan Provincial Maternal and Child Health Care Hospital, changsha, Hunan, 410008, Department of Anesthesiology, the Second Affiliated Hospital of University of South China, Hengyang, Hunan, 421001



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