國家衛生研究院 NHRI:Item 3990099045/9934
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9934


    Title: Thiostrepton inhibits psoriasis-like inflammation induced by TLR7, TLR8, and TLR9
    Authors: Lai, CY;Yeh, DW;Lu, CH;Liu, YL;Huang, LR;Kao, CY;Chen, HY;Huang, CYF;Chang, CH;Luo, YP;Xiang, R;Chuang, TH
    Contributors: Immunology Research Center;Institute of Molecular and Genomic Medicine
    Abstract: Toll-like receptors 7, 8 and 9 (TLR7-9) comprise a subfamily of TLR. Activation of these TLRs has been linked to the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. Thus antagonists of these TLRs are being investigated for their therapeutic applications on these diseases. Bortezomib is a proteasome inhibitor known to suppress activation of these TLRs. This drug is approved for the treatment of multiple myeloma, and its inhibitory effects on autoimmune disorders such as psoriasis, RA, and SLE have also been investigated in animal models. In an attempt to develop novel TLR7-9 inhibitors, we searched the Gene Expression Omnibus database for gene expression profiles in cells treated with bortezomib. These profiles were then used as an input to screen the Connectivity Map database for chemical compounds with similar functions as bortezomib. Here we report that the antibiotic thiostrepton is a novel TLR7–9 inhibitor. Like bortezomib, thiostrepton effectively inhibits TLR7–9 activation in cell-based assays and dendritic cells. In contrast to bortezomib, thiostrepton is less cytotoxic to dendritic cells, and its inhibitory activity is more specific to TLR7–9. Thiostrepton inhibits TLR9 localization in endosomes for activation via two mechanisms. One mechanism is similar to the proteasome inhibitory function of bortezomib, and the other is through inhibition of endosomal acidification. In different animal models, thiostrepton attenuated LL37- and imiquimod-induced psoriasis-like inflammation. These results indicated that thiostrepton is a novel and specific inhibitor to TLR7–9.
    Date: 2016-05
    Relation: Journal of Immunology. 2016 May;196(1 Suppl.):Meeting Abstract 124.41.
    Link to: http://www.jimmunol.org/content/196/1_Supplement/124.41
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000380288300077
    Appears in Collections:[Tsung-Hsien Chuang] Conference Papers/Meeting Abstract
    [Cheng-Yuan Gao] Conference Papers/Meeting Abstract
    [Li-Rung Huang] Conference Papers/Meeting Abstract

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