Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Suppression of the TRIF-Dependent Signaling Pathway of Toll-Like Receptors by Isoliquiritigenin in RAW264.7 Macrophages

  • Park, Se-Jeong (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University) ;
  • Song, Ho-Yeon (Department of Microbiology, School of Medicine, Soonchunhyang University) ;
  • Youn, Hyung-Sun (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University)
  • Received : 2009.05.25
  • Accepted : 2009.08.17
  • Published : 2009.10.31
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Abstract

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

Keywords

References

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