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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Suppression of the TRIF-dependent signaling pathway of toll-like receptors by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate

  • Park, Se-Jeong (Department of Medical Science, Soonchunhyang University) ;
  • Park, Hye-Jeong (Department of Biomedical Laboratory Science, Soonchunhyang University) ;
  • Kim, Soo-Jung (Department of Biomedical Laboratory Science, Soonchunhyang University) ;
  • Shin, Hwa-Jeong (Department of Medical Science, Soonchunhyang University) ;
  • Min, In-Soon (Department of Healthcare Management, College of Medical Sciences, Soonchunhyang University) ;
  • Koh, Kwang-Oh (Department of Chemistry, College of Natural Sciences, Soonchunhyang University) ;
  • Kim, Dae-Young (Department of Chemistry, College of Natural Sciences, Soonchunhyang University) ;
  • Youn, Hyung-Sun (Department of Medical Science, Soonchunhyang University)
  • Received : 2011.04.06
  • Accepted : 2011.05.13
  • Published : 2011.07.31
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Abstract

Toll-like receptors (TLRs) are pattern recognition receptors that recognize molecular structures derived from microbes and initiate innate immunity. TLRs have two downstream signaling pathways, the MyD88- and TRIF-dependent pathways. Dysregulated activation of TLRs is closely linked to increased risk of many chronic diseases. Previously, we synthesized fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate (IPOP), which contains a fumaric acid isopropyl ester and pyrrolidinone, and demonstrated that it inhibits the activation of nuclear factor kappa B by inhibiting the MyD88-dependent pathway of TLRs. However, the effect of IPOP on the TRIF-dependent pathway remains unknown. Here, we report the effect of IPOP on signal transduction via the TRIF-dependent pathway of TLRs. IPOP inhibited lipopolysaccharide- or polyinosinic-polycytidylic acidinduced interferon regulatory factor 3 activation, as well as interferon-inducible genes such as interferon inducible protein-10. These results suggest that IPOP can modulate the TRIF-dependent signaling pathway of TLRs, leading to decreased inflammatory gene expression.

Keywords

References

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