lobolideaditerpeneblockadesthenfbpathwayandp38anderkmapkactivityinmacrophagesinvitro

	lobolideaditerpeneblockadesthenfbpathwayandp38anderkmapkactivityinmacrophagesinvitro
	Lv Xiaofen; Chen Sihan; Li Jie; Fang Jianping; Guo Yuewei; Ding Kan
刊名	actapharmacologicasinica
	2012
卷号	033 期号:010 页码:1293
关键词	巨噬细胞 MAPK ERK p38 通路二萜封锁活性
ISSN号	1671-4083
英文摘要	Aim： Recent studies have shown that constitutive activation of the nuclear factor κB （NF-κB） 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-κB signaling pathway. Methods： A HEK 293/NF-κB-luc stable cell line was constructed to evaluate the effect of lobolide on NF-κB activation. THP-1 human monocytes and peripheral blood mononuclear cells （PBMCs） from healthy volunteers were tested. Lipopolysaccharide （LPS）-induced TNFα and IL-1β production and activation of the TAK1-IKK-NF-κB pathway were studied using ELISA and Western blot analysis.Results： In HEK 293/NF-κB-luc stable cells, lobolide （0.19–50 μmol/L） inhibited NF-κB activation in a concentration-dependent manner with an IC50 value of 4.2±0.3 μmol/L. Treatment with lobolide （2.5–10 μmol/L） significantly suppressed LPS-induced production of TNFα and IL-1β in both THP-1 cells and PBMCs. In THP-1 cells, the suppression was partially caused by blockade of the translocation of NF-κB from the cytoplasm to the nucleus via affecting the TAK1-IKK-NF-κB pathway and p38 and ERK MAPK activity.Conclusion： Lobolide is a potential inhibitor of the NF-κB pathway, which blocks the translocation of NF-κB from the cytoplasm to the nucleus. Lobolide inhibits LPS-stimulated TNFα and IL-1β release, suggesting that the compound might be an anti-inflammatory compound.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/286062]
专题	中国科学院上海药物研究所
作者单位	中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Lv Xiaofen,Chen Sihan,Li Jie,et al. lobolideaditerpeneblockadesthenfbpathwayandp38anderkmapkactivityinmacrophagesinvitro[J]. actapharmacologicasinica,2012,033(010):1293.
APA	Lv Xiaofen,Chen Sihan,Li Jie,Fang Jianping,Guo Yuewei,&Ding Kan.(2012).lobolideaditerpeneblockadesthenfbpathwayandp38anderkmapkactivityinmacrophagesinvitro.actapharmacologicasinica,033(010),1293.
MLA	Lv Xiaofen,et al."lobolideaditerpeneblockadesthenfbpathwayandp38anderkmapkactivityinmacrophagesinvitro".actapharmacologicasinica 033.010(2012):1293.