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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume339
Issue number1
DOIs
Publication statusPublished - Jan 6 2006

Fingerprint

Dioscorea
Toll-Like Receptor 4
Macrophages
Cytokines
Plant Structures
Inbred C3H Mouse
Screening
Medicinal Plants
Polymyxin B
Macrophage Activation
Immune System Diseases
Adaptive Immunity
Interleukin-1
Innate Immunity
Bone Marrow Cells
Interleukin-6
Glycoproteins
Bone
Contamination
Chemical activation

Keywords

  • Cytokine
  • Dioscorea alata
  • Dioscorin
  • MAPK
  • NF-κB
  • TLR4

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages. / Fu, Shu Ling; Hsu, Ya Hui; Lee, Pei Yeh; Hou, Wen Chi; Hung, Ling Chien; Lin, Chao Hsiung; Chen, Chiu Ming; Huang, Yu Jing.

In: Biochemical and Biophysical Research Communications, Vol. 339, No. 1, 06.01.2006, p. 137-144.

Research output: Contribution to journalArticle

Fu, Shu Ling ; Hsu, Ya Hui ; Lee, Pei Yeh ; Hou, Wen Chi ; Hung, Ling Chien ; Lin, Chao Hsiung ; Chen, Chiu Ming ; Huang, Yu Jing. / Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 339, No. 1. pp. 137-144.
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