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Suppression of the TRIF-dependent signaling pathway of toll-like receptor by triptolide

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Abstract

Toll-like receptors (TLRs) recognize specific patterns derived from invading microbial pathogens. TLR activation by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and tollinterleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent downstream signaling pathways, leading to the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3). Triptolide (TP), an active ingredient of Tripterygium wilfordii Hook. F, has been reported to have positive effects on autoimmune and inflammatory diseases. To evaluate the therapeutic potential of TP, its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]) was examined. TP inhibited NF-κB and IRF3 activation and IRF3 phosphorylation induced by LPS or poly[I:C]. TP also inhibited interferon-inducible genes such as, interferon inducible protein-10. These results suggest that TP can modulate TRIF-dependent signaling pathways of TLRs, and will become promising drug candidates in TLRs-based therapy in the future.

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Authors and Affiliations

  1. Department of Medical Science, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Korea

    Gyo-Jeong Gu & Hyung-Sun Youn

  2. Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, 336-745, Korea

    Hyung-Sun Youn

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  1. Gyo-Jeong Gu
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Correspondence to Hyung-Sun Youn.

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Gu, GJ., Youn, HS. Suppression of the TRIF-dependent signaling pathway of toll-like receptor by triptolide. Toxicol. Environ. Health Sci. 5, 177–182 (2013). https://doi.org/10.1007/s13530-013-0173-6

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  • DOI: https://doi.org/10.1007/s13530-013-0173-6

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