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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
- Source :
- Current Molecular Pharmacology. 14:914-921
- Publication Year :
- 2021
- Publisher :
- Bentham Science Publishers Ltd., 2021.
-
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.
- Subjects :
- Inflammasomes
Autophagy
NF-kappa B
Priming (immunology)
Inflammasome
NF-κB
General Medicine
Cell biology
Proinflammatory cytokine
PPAR gamma
Blot
chemistry.chemical_compound
chemistry
Diarylheptanoids
NLR Family, Pyrin Domain-Containing 3 Protein
Curcumin
medicine
Phosphorylation
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 18744672
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Current Molecular Pharmacology
- Accession number :
- edsair.doi.dedup.....eab7412b6f14ee9acb60e1d124baa497