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Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.33 no.6, 2010년, pp.939 - 945   SCIE
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TBK1-Targeted Suppression of TRIF-Dependent Signaling Pathway of Toll-like Receptor 3 by Auranofin

Park, Se-Jeong    (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University   ); Lee, A-Neum    (Departments of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University   ); Youn, Hyung-Sun    (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University  );
  • 초록

    Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The stimulation of TLRs by microbial components triggers two branches of downstream signaling pathways: myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon- ${\beta}$ (TRIF)-dependent signaling pathways. Auranofin, a sulfur-containing gold compound (Au[I]), has been widely used for the treatment of rheumatoid arthritis. Since dysregulation of TLRs can lead to severe systemic inflammatory and joint destructive process in rheumatoid arthritis, auranofin-mediated modulation of TLR activation may have therapeutic potential against such diseases. Previously, we demonstrated that auranofin suppressed TLR4 signaling pathway by inhibiting TLR4 dimerization induced by LPS. Here, we examined the effect of auranofin on signal transduction via the TRIFdependent pathway induced by a TLR3 agonist. Auranofin inhibited nuclear factor-kB and interferon (IFN) regulatory factor 3 (IRF3) activation induced by polyinosinic-polycytidylic acid (poly[I:C]). Auranofin inhibited poly[I:C]-induced phosphorylation of IRF3 as well as IFNinducible genes such as IFN inducible protein-10. Furthermore, auranofin inhibited TBK1 kinase activity in vitro. All the results suggest that auranofin suppress TLR signaling at multiple steps.

  • 주제어

    Toll-like receptors .   Auranofin .   Poly[I:C] .   TRIF .   TBK1 .   IRF3.  

  • 참고문헌 (24)

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    2. 2009 "Isoliquiritigenin의 toll-like receptor agonists에 의해서 유도된 NF-${\kappa}$B 활성화와 cyclooxygenase-2 발현 억제" 한국식품과학회지 = Korean journal of food science and technology 41 (2): 220~224    
    3. 2009 "Oak Wood Vinegar Suppresses the Expression of Cyclooxygenase-2 Induced by TLR4 Agonist" Journal of experimental & biomedical sciences = 대한의생명과학회지 15 (3): 257~260    
    4. 2010 "Suppression of TRIF-dependent signaling pathway of Toll-like receptors by oak wood vinegar in RAW264.7 macrophages" Molecular & cellular toxicology 6 (1): 73~78    
    5. 2011 "Ovalbumin에 의한 cyclooxygenase-2와 inducible nitric oxide synthase 유도" 한국식품과학회지 = Korean journal of food science and technology 43 (1): 110~113    
    6. 2011 "Suppression of the TRIF-dependent signaling pathway of toll-like receptors by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate" BMB reports 44 (7): 468~472    
    7. 2011 "Suppression of cyclooxygenase-2 expression induced by Toll-like receptor 2 or 4 agonists by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate" Molecular & cellular toxicology 7 (1): 39~44    
  • 이아늠 (4)

  • Youn, Hyung-Sun (29)

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