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Lobolide, a diterpene, blockades the NF-kappa B pathway and p38 and ERK MAPK activity in macrophages in vitro

文献类型：期刊论文

作者Lv, Xiao-fen2; Chen, Si-han1; Li, Jie2; Fang, Jian-ping2; Guo, Yue-wei1; Ding, Kan2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2012-10
卷号33期号:10页码:1293-1300
关键词lobolide diterpene monocytes lipopolysaccharide NF-kappa B TNF alpha IL-1 beta TAK1 Erk 1/2 p38 inflammation
ISSN号1671-4083
DOI10.1038/aps.2012.100
文献子类Article
英文摘要Aim: Recent studies have shown that constitutive activation of the nuclear factor kappa B (NF-kappa B) plays a key role in chronic inflammation and cancers. The aim of this study was to characterize lobolide, a cembrane diterpene, as a drug candidate targeting the NF-kappa B signaling pathway. Methods: A HEK 293/NF-kappa B-luc stable cell line was constructed to evaluate the effect of lobolide on NF-kappa B activation. THP-1 human monocytes and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were tested. Lipopolysaccharide (LPS)-induced TNF alpha and IL-1 beta production and activation of the TAK1-IKK-NF-kappa B pathway were studied using ELISA and Western blot analysis. Results: In HEK 293/NF-kappa B-Luc stable cells, lobolide (0.19-50 mu mol/L) inhibited NF-kappa B activation in a concentration-dependent manner with an IC50 value of 4.2 +/- 0.3 mu mol/L. Treatment with lobolide (2.5-10 mu mol/L) significantly suppressed LPS-induced production of TNF alpha and IL-1 beta in both THP-1 cells and PBMCs. In THP-1 cells, the suppression was partially caused by blockade of the translocation of NF-kappa B from the cytoplasm to the nucleus via affecting the TAK1-IKK-NF-kappa B pathway and p38 and ERK MAPK activity. Conclusion: Lobolide is a potential inhibitor of the NF-kappa B pathway, which blocks the translocation of NF-kappa B from the cytoplasm to the nucleus. Lobolide inhibits LPS-stimulated TNF alpha and IL-1 beta release, suggesting that the compound might be an anti-inflammatory compound.
WOS关键词NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; PROTEIN-KINASE ; LIPOPOLYSACCHARIDE ; ACTIVATION ; CELLS ; TAK1 ; MECHANISMS ; INHIBITORS ; CYTOKINES ; RESPONSES
资助项目National Natural Science Foundation of China[30870551] ; Key New Drug Creation and Manufacturing Program of China[2009ZX09501-011] ; Key New Drug Creation and Manufacturing Program of China[2009ZX09103-071] ; Key New Drug Creation and Manufacturing Program of China[2009ZX09301-001]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:4639822
WOS记录号WOS:000309656500008
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/277931]  
专题天然药物化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药理学第三研究室
通讯作者Guo, Yue-wei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Glycochem & Glycobiol Lab, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Lv, Xiao-fen,Chen, Si-han,Li, Jie,et al. Lobolide, a diterpene, blockades the NF-kappa B pathway and p38 and ERK MAPK activity in macrophages in vitro[J]. ACTA PHARMACOLOGICA SINICA,2012,33(10):1293-1300.
APA Lv, Xiao-fen,Chen, Si-han,Li, Jie,Fang, Jian-ping,Guo, Yue-wei,&Ding, Kan.(2012).Lobolide, a diterpene, blockades the NF-kappa B pathway and p38 and ERK MAPK activity in macrophages in vitro.ACTA PHARMACOLOGICA SINICA,33(10),1293-1300.
MLA Lv, Xiao-fen,et al."Lobolide, a diterpene, blockades the NF-kappa B pathway and p38 and ERK MAPK activity in macrophages in vitro".ACTA PHARMACOLOGICA SINICA 33.10(2012):1293-1300.

入库方式： OAI收割

来源：上海药物研究所

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