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KMID : 0578320090270020211
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Molecules and Cells
2009 Volume.27 No. 2 p.211 ~ p.215
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Inhibition of Homodimerization of Toll-like Receptor 4 by 6-Shogaol
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Ahn Sang-Il
Lee Jun-Kyung
Youn Hyung-Sun
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Abstract
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Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B (NF-?첕). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report bio-chemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced di-merization of TLR4 resulting in the inhibition of NF-?첕 activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.
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KEYWORD
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cyclooxygenase-2, dimerization, lipopolysaccharide, NF-κB, toll like receptors
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