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Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination
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 o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439433/ https://www.ncbi.nlm.nih.gov/pubmed/22984582 http://dx.doi.org/10.1371/journal.pone.0044890 |
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author | Chen, Qiang Chen, Tenghui Li, Wenjiao Zhang, Wei Zhu, Jingwei Li, Yang Huang, Yaojian Shen, Yuemao Yu, Chundong |
author_facet | Chen, Qiang Chen, Tenghui Li, Wenjiao Zhang, Wei Zhu, Jingwei Li, Yang Huang, Yaojian Shen, Yuemao Yu, Chundong |
author_sort | Chen, Qiang |
collection | PubMed |
description | 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-α (TNF-α), interleukin (IL)-1β, IL-6, and nitric oxide (NO) in macrophages. MED inhibited LPS-induced nuclear translocation of nuclear factor (NF)-κB (NF-κB) p65, IκB degradation, IκB 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-κB 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-β–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 anti-inflammatory drug. |
format | Online Article Text |
id | pubmed-3439433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34394332012-09-14 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 Shen, Yuemao Yu, Chundong PLoS One Research Article 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-α (TNF-α), interleukin (IL)-1β, IL-6, and nitric oxide (NO) in macrophages. MED inhibited LPS-induced nuclear translocation of nuclear factor (NF)-κB (NF-κB) p65, IκB degradation, IκB 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-κB 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-β–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 anti-inflammatory drug. Public Library of Science 2012-09-11 /pmc/articles/PMC3439433/ /pubmed/22984582 http://dx.doi.org/10.1371/journal.pone.0044890 Text en © 2012 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chen, Qiang Chen, Tenghui Li, Wenjiao Zhang, Wei Zhu, Jingwei Li, Yang Huang, Yaojian Shen, Yuemao Yu, Chundong Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title | Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title_full | Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title_fullStr | Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title_full_unstemmed | Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title_short | Mycoepoxydiene Inhibits Lipopolysaccharide-Induced Inflammatory Responses through the of TRAF6 Polyubiquitination |
title_sort | mycoepoxydiene inhibits lipopolysaccharide-induced inflammatory responses through the of traf6 polyubiquitination |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439433/ https://www.ncbi.nlm.nih.gov/pubmed/22984582 http://dx.doi.org/10.1371/journal.pone.0044890 |
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