國家衛生研究院 NHRI:Item 3990099045/1639
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1639


    Title: Irbesartan inhibits human T-lymphocyte activation through downregulation of activator protein-1
    Authors: Cheng, SM;Yang, SP;Ho, LJ;Tsao, TP;Chang, DM;Lai, JH
    Contributors: Division of Gerontology Research
    Abstract: 1 Irbesartan is a promising anti hypertensive drug with beneficial effects on atherosclerotic processes. In the progression of atherosclerosis, human T-lymphocytes play an important role, but it is not yet known how irbesartan modulates human T-lymphocytes activation. To gain insight into the mechanisms by which irbesartan acts, we investigated its effects on human T-lymphocytes. 2 Primary human T-lymphocytes were isolated from whole blood. Cytokines were determined by ELISA. Activator protein-1 (AP-1) and related protein activities were determined by electrophoretic mobility shift assays, kinase assays, Western blotting and transfection assays. 3 Irbesartan inhibited the production of both tumor necrosis factor-alpha and interferon-gamma by activated T-cells, especially at therapeutic concentrations. Further investigation at the molecular level indicated that the inhibition of activated human T-lymphocytes specifically correlated with the downregulation of AP-1 DNA-binding activity. In the Jurkat T-cell line, irbesartan also inhibited AP-1 transcriptional activity. Finally, we revealed that irbesartan is unique in its ability to inhibit the activation of both c-Jun NH2-terminal protein kinase and p38 MAPK. 4 Our studies show that irbesartan may modulate inflammation-based atherosclerotic diseases through a cell-mediated mechanism involving suppression of human T-lymphocytes activation via downregulation of AP-1 activity.
    Keywords: Pharmacology & Pharmacy
    Date: 2004-07
    Relation: British Journal of Pharmacology. 2004 Jul;142(6):933-942.
    Link to: http://dx.doi.org/10.1038/sj.bjp.0705785
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-1188&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000222937500003
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=3843096209
    Appears in Collections:[Ling-Jun Ho] Periodical Articles

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