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	Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination
	Chen, Qiang ; Chen, Tenghui ; Li, Wenjiao ; Zhang, Wei ; Zhu, Jingwei ; Li, Yang ; Huang, Yaojian ; Huang YJ(黄耀坚) ; Shen, Yuemao ; Yu, Chundong
	2012-09-11
关键词	NITRIC-OXIDE SYNTHASE TOLL-LIKE RECEPTORS INNATE IMMUNITY MAP KINASE INTERLEUKIN-1 METABOLITES METABOLITES PATHWAY P38
英文摘要	Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. MED has been shown to be able to induce cell cycle arrest and cancer cell apoptosis. However, its effects on inflammatory response are unclear. Herein we showed that MED exhibited inhibitory effect on inflammatory response induced by lipopolysaccharide (LPS). MED significantly inhibited LPS-induced expression of pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, and nitric oxide (NO) in macrophages. MED inhibited LPS-induced nuclear translocation of nuclear factor (NF)-kappa B (NF-kappa B) p65, I kappa B degradation, I kappa B kinase (IKK) phosphorylation, and the activation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38, suggesting that MED blocks the activation of both NF-kappa B and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the effects of MED on LPS-induced activation of upstream signaling molecules such as transforming growth factor-beta-activated kinase 1 (TAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor associated kinases1 (IRAK1) were investigated. MED significantly inhibited TAK1 phosphorylation and TRAF6 polyubiquitination, but not IRAK1 phosphorylation and TRAF6 dimerization, indicating that MED inhibits LPS-induced inflammatory responses at least in part through suppression of TRAF6 polyubiquitination. Moreover, MED protected mice from LPS-induced endotoxin shock by reducing serum inflammatory cytokines. These results suggest that MED is a potential lead compound for the development of a novel nonsteroidal antiinflammatory drug.; National Basic Research Program of China (973 Program) [2009CB522200, 2010CB833802]; Natural Science Foundation of Fujian Province of China [2010J06014]; Natural Science Foundation of China [31170819, 90913024]; Youth Foundation of Health Department of Fujian Province [2010-2-84]
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1371/journal.pone.0044890]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Chen, Qiang,Chen, Tenghui,Li, Wenjiao,et al. Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination[J],2012.
APA	Chen, Qiang.,Chen, Tenghui.,Li, Wenjiao.,Zhang, Wei.,Zhu, Jingwei.,...&Yu, Chundong.(2012).Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination..
MLA	Chen, Qiang,et al."Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination".(2012).

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