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Updated: Feb 21, 2026
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation
Xianjun Yu1,2, Qun Zhao1, Xixi Zhang1
1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Abstract:
Celastrol exhibits potential anti-inflammatory activity in a variety of inflammatory diseases, but the mechanism remains poorly understood. Activation of NLRP3 inflammasome is involved in multiple inflammatory diseases. Here, we show that celastrol abolishes the NLRP3 inflammasome activation, inhibits subsequent caspase-1 activation and IL-1β secretion both in vitro and in vivo. Notably, interruption of ASC oligomerization and autophagy activation are involved in NLRP3 inflammasome inactivation by celastrol. Importantly, in vivo results indicate that celastrol attenuates NLRP3 inflammasome-dependent inflammation diseases via autophagy-related pathway. Our results thus reveal celastrol as an inhibitor of NLRP3 inflammasome, implying the potential for clinical use of celastrol in treatment of NLRP3 inflammasome-driven inflammatory diseases.
Insights
Celastrol inhibits the NLRP3 inflammasome, a key driver of inflammation. This compound reduces inflammatory responses by impacting ASC oligomerization and activating autophagy, suggesting potential for treating inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- The NLRP3 inflammasome plays a critical role in inflammatory diseases.
- Celastrol has shown potential anti-inflammatory effects, but its mechanism is unclear.
Purpose of the Study:
- To investigate the mechanism by which celastrol exerts its anti-inflammatory activity.
- To determine if celastrol affects NLRP3 inflammasome activation.
Main Methods:
- In vitro and in vivo studies were conducted.
- Assessed NLRP3 inflammasome activation, caspase-1 activation, IL-1β secretion, ASC oligomerization, and autophagy.
- Evaluated celastrol's effects in inflammatory disease models.
Main Results:
- Celastrol effectively inhibited NLRP3 inflammasome activation, caspase-1 activation, and IL-1β secretion.
- Celastrol interrupted ASC oligomerization and promoted autophagy.
- In vivo, celastrol attenuated inflammation in NLRP3-dependent disease models via autophagy.
Conclusions:
- Celastrol functions as an inhibitor of the NLRP3 inflammasome.
- Celastrol's anti-inflammatory effects are mediated through the autophagy pathway.
- Celastrol holds promise for treating inflammatory diseases driven by the NLRP3 inflammasome.
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