Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages

Shu Ling Fu, Ya Hui Hsu, Pei Yeh Lee, Wen Chi Hou, Ling Chien Hung, Chao Hsiung Lin, Chiu Ming Chen, Yu Jing Huang

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

The Toll-like receptor 4 (TLR4)-signaling pathway is crucial for activating both innate and adaptive immunity. TLR4 is a promising molecular target for immune-modulating drugs, and TLR4 agonists are of therapeutic potential for treating immune diseases and cancers. Several medicinal herb-derived components have recently been reported to act via TLR4-dependent pathways, suggesting that medicinal plants are potential resources for identifying TLR4 activators. We have applied a screening procedure to systematically identify herbal constituents that activate TLR4. To exclude possible LPS contamination in these plant-derived components, a LPS inhibitor, polymyxin B, was added during screening. One of the plant components we identified from the screening was dioscorin, the glycoprotein isolated from Dioscorea alata. It induced TLR4-downstream cytokine expression in bone marrow cells isolated from TLR4-functional C3H/HeN mice but not from TLR4-defective C3H/HeJ mice. Dioscorin also stimulated multiple signaling molecules (NF-κB, ERK, JNK, and p38) and induced the expression of cytokines (TNF-α, IL-1β, and IL-6) in murine RAW 264.7 macrophages. Furthermore, the ERK, p38, JNK, and NF-κB-mediated pathways are all involved in dioscorin-mediated TNF-α production. In summary, our results demonstrate that dioscorin is a novel TLR4 activator and induces macrophage activation via typical TLR4-signaling pathways.

原文英語
頁(從 - 到)137-144
頁數8
期刊Biochemical and Biophysical Research Communications
339
發行號1
DOIs
出版狀態已發佈 - 一月 6 2006

ASJC Scopus subject areas

  • 生物化學
  • 生物物理學
  • 分子生物學

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