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 language | English |
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Pages (from-to) | 137-144 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 339 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 6 2006 |
Keywords
- Cytokine
- Dioscorea alata
- Dioscorin
- MAPK
- NF-κB
- TLR4
ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Biochemistry
- Cell Biology