Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination
Zhao, Xibao1,2; Pu, Debing3,4; Zhao, Zizhao2; Zhu, Huihui2; Li, Hongrui1,2; Shen, Yaping2; Zhang, Xingjie3; Zhang, Ruihan3; Shen, Jianzhong5; Xiao, Weilie3,4; Chen, Weilin1,2
2017-08-23
发表期刊FRONTIERS IN PHARMACOLOGY
ISSN1663-9812
卷号8页码:565
摘要Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines production and NLRP3 inflammasome activation. Our results showed that Teuvincenone F attenuated K63-linked ubiquitination of NF-kappa B-essential modulator (NEMO, also known as IKK gamma) to suppress LPS-induced phosphorylation of NF-kappa B, and inhibited mRNA expression of IL-1 beta, IL-6, TNF-alpha, and NLRP3. In addition, we found that decreased NLRP3 expression by Teuvincenone F suppressed NLRP3 inflammasome activation and IL-1 beta/IL-18 maturation. In vivo, we revealed that Teuvincenone F treatment relieved LPS-induced inflammation. In conclusion, Teuvincenone F is a highly effective natural compound to suppress LPS-induced inflammation by attenuating K63-linked ubiquitination of NEMO, highlighting that Teuvincenone F may be a potential new anti-inflammatory drug for the treatment of inflammatory and NLRP3 inflammasome-driven diseases.
关键词Teuvincenone f Inflammation Nlrp3 Inflammasome Ubiquitination Nemo
学科领域Pharmacology & Pharmacy
DOI10.3389/fphar.2017.00565
收录类别SCI
语种英语
WOS记录号WOS:000408517500001
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/54914
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Shenzhen Univ, Dept Immunol, Sch Med, Shenzhen, Peoples R China
2.Zhejiang Univ, Inst Immunol, Dept Basic Med, Sch Med, Hangzhou, Zhejiang, Peoples R China
3.Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Sch Chem Sci & Technol, Kunming, Yunnan, Peoples R China
4.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming, Yunnan, Peoples R China
5.Auburn Univ, Dept Drug Discovery & Dev, Harrison Sch Pharm, Auburn, AL 36849 USA
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Zhao, Xibao,Pu, Debing,Zhao, Zizhao,et al. Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination[J]. FRONTIERS IN PHARMACOLOGY,2017,8:565.
APA Zhao, Xibao.,Pu, Debing.,Zhao, Zizhao.,Zhu, Huihui.,Li, Hongrui.,...&Chen, Weilin.(2017).Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination.FRONTIERS IN PHARMACOLOGY,8,565.
MLA Zhao, Xibao,et al."Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination".FRONTIERS IN PHARMACOLOGY 8(2017):565.
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