國家衛生研究院 NHRI:Item 3990099045/12420
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    题名: Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1alpha
    其它题名: Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1α
    作者: Lee, YZ;Guo, HC;Zhao, GH;Yang, CW;Chang, HY;Yang, RB;Chen, L;Lee, SJ
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Interruption of the Warburg effect - the observation that un-stimulated macrophages reprogram their core metabolism from oxidative phosphorylation toward aerobic glycolysis to become pro-inflammatory M1 macrophages upon stimulation - is an emerging strategy for the treatment of cancer and anti-inflammatory diseases such as rheumatoid arthritis. We studied this process with view to the discovery of novel therapeutics, and found that tylophorine-based compounds targeted a ribonucleoprotein complex containing caprin-1 and mRNAs of c-Myc and HIF-1alpha in LPS/IFN-gamma stimulated Raw264.7 cells, diminished the protein levels of c-Myc and HIF-1alpha, and consequently downregulated their targeted genes that are associated with the Warburg effect, as well as the pro-inflammatory iNOS and COX2. The tylophorine-based compound DBQ 33b significantly meliorated the severity and incidence of type II collagen-monoclonal antibody-induced rheumatoid arthritis and diminished gene expressions of c-Myc, HIF-1alpha, iNOS, COX2, TNFalpha, and IL-17A in vivo. Moreover, pharmacological inhibition of either c-Myc or HIF-1alpha exhibited similar effects as the tylophorine-based compound DBQ 33b, even though inhibition of c-Myc reversed the induction of iNOS and COX2 in LPS/IFN-gamma stimulated Raw264.7 cells to a lesser degree. Therefore, simultaneous inhibition of both c-Myc and HIF-1alpha is efficacious for anti-inflammation in vitro and in vivo and merits further study.
    日期: 2020-02
    關聯: Pharmacological Research. 2020 Feb;152:Article number 104581.
    Link to: http://dx.doi.org/10.1016/j.phrs.2019.104581
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1043-6618&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000518700200030
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85076135438
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