Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells.

Abstract

Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL's anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

• Authors: Xianghong Lei, Shuting Li, Congwei Luo, Yuxian Wang, Yanxia Liu, Zhaozhong Xu, Qianyin Huang, Fangqin Zou, Yihua Chen, Fenfen Peng, Haibo Long
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2020 Pg. 3934769 ( 2020) ISSN: 1466-1861 [Electronic] United States
• PMID: 32879619 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Xianghong Lei et al.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Carrier Proteins
• Cytokines
• Inflammasomes
• Lipopolysaccharides
• NF-kappa B p50 Subunit
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Reactive Oxygen Species
• Sesquiterpenes, Guaiane
• Tetrazolium Salts
• Thiazoles
• micheliolide
• thiazolyl blue

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Carrier Proteins (metabolism)
• Cell Line
• Cytokines (metabolism)
• Epithelial Cells (metabolism)
• Inflammasomes
• Inflammation
• Kidney Tubules (cytology)
• Lipopolysaccharides (metabolism)
• NF-kappa B p50 Subunit (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Rats
• Reactive Oxygen Species
• Sesquiterpenes, Guaiane (pharmacology)
• Signal Transduction (drug effects)
• Tetrazolium Salts (chemistry)
• Thiazoles (chemistry)