Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Inhibition of Homodimerization of Toll-like Receptor 4 by 6-Shogaol

  • Ahn, Sang-Il (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University) ;
  • Lee, Jun-Kyung (Cell Culture Process Research and Development Center, Celltrion Inc.) ;
  • Youn, Hyung-Sun (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University)
  • Received : 2008.10.30
  • Accepted : 2008.12.01
  • Published : 2009.02.28
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Abstract

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 ($NF-{\kappa}B$). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of $NF-{\kappa}B$ 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.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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