國家衛生研究院 NHRI:Item 3990099045/10733
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    題名: Thiostrepton inhibits Toll-like receptors 7, 8 and 9 mediated inflammatory responses
    作者: Chuang, TH;Lai, CY;Yeh, DW;Lu, CH;Liu, YL
    貢獻者: Immunology Research Center
    摘要: Toll-like receptors (TLRs) play a key role in sensing pathogen-associated molecular patterns for initiating immune responses against microbial infections. Ten TLRs are identified in human cells. Of them, TLRs 7, 8 and 9 (TLR7-9) comprise a subfamily. Activation of these three TLRs has been linked to the pathogenesis of autoimmune diseases including psoriasis. Thus antagonists of these TLRs are being investigated for their therapeutic applications on these diseases. 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 which is known as an inhibitor for TLR7-9. These profiles were then used as an input to screen the Connectivity Map database for chemical compounds with similar functions as bortezomib. The result suggest that the antibiotic thiostrepton could has similar function as bortezomib in inhibition of TLR7–9. Further studies showed that 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. In different animal models, thiostrepton attenuated LL37- and imiquimod-induced psoriasis-like inflammation. These results indicated that thiostrepton is a novel inhibitor for TLR7–9.
    日期: 2016-04
    關聯: The FASEB Journal. 2016 Apr;30(1, Suppl.):Meeting Abstract lb453.
    Link to: http://www.fasebj.org/content/30/1_Supplement/lb453?related-urls=yes&legid=fasebj;30/1_Supplement/lb453
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0892-6638&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000406444700006
    顯示於類別:[莊宗顯] 會議論文/會議摘要

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