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Eur J Pharmacol. 2017 Nov 5;814:240-247. doi: 10.1016/j.ejphar.2017.08.036. Epub 2017 Aug 30.

A new mechanism of inhibition of IL-1β secretion by celastrol through the NLRP3 inflammasome pathway.

Author information

1
Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai 264003, PR China; Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai 264005, PR China. Electronic address: xinwenyu1391139@163.com.
2
Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai 264003, PR China. Electronic address: wqy196911@163.com.
3
Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, PR China. Electronic address: dan1216@163.com.
4
Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai 264003, PR China. Electronic address: ytwcy@163.com.

Abstract

The NLRP3 (NOD-like receptor protein 3) inflammasome is a caspase-1-containing multiprotein complex that controls the release of IL-1β and has been associated with the development of inflammatory diseases. Celastrol, a pharmacologically active ingredient extracted from Tripterygium wilfordii Hook, has anti-inflammatory activities based on its inhibition of IL-1β secretion. The purpose of the present study was to investigate the possible modulation of NLRP3 inflammasome-mediated IL-1β and IL-18 release from macrophages by celastrol. It was shown that celastrol significantly reduced the secretion of IL-1β and IL-18 by inhibiting the expression of NLRP3 and the cleavage of caspase-1 in lipopolysaccharide (LPS)/ATP-induced macrophages. In addition, celastrol suppressed pyroptosis in macrophages, demonstrated by caspase-1 activation, LDH leakage and PI uptake assays. Furthermore, these inhibitory effects of celastrol were found to be at least partially achieved by decreasing the up-regulation of reactive oxygen species generation and NF-κB activation. Taken together, these findings suggested a new anti-inflammation mechanism of celastrol through inhibition of the NLRP3 inflammasome.

KEYWORDS:

Anti-inflammatory effects; Celastrol; IL-1β; NLRP3 inflammasome

PMID:
28864208
DOI:
10.1016/j.ejphar.2017.08.036
[Indexed for MEDLINE]

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