國家衛生研究院 NHRI:Item 3990099045/9824
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    題名: sn-1,2-diacylglycerols protect against lethal endotoxemia by controlling systemic inflammation
    作者: Wang, YF;Lee, GL;Huang, YH;Kuo, CC
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Systemic inflammation has emerged as a key pathophysiological process that induces multiple organ injuries and causes serious human diseases. Despite substantial evidence supporting the role of diacylglycerols (DAG) in modulating chronic inflammation and chronic diseases, the potential mechanisms of its involvement in TLRs-mediated inflammation are still unclear. Here, we show that sn-1,2-diacylglycerols modulate LPS/TLR4-mediated inflammation in vitro and in vivo. ELISA and western blotting experiments indicated that sn-1,2-diacylglycerols suppress LPS-induced responses, including IL-6 and TNF-α production, and COX-2 expression in mouse RAW264.7 macrophages and human endothelial cells, in a dose-dependent manner. Using LPS-induced murine model of systemic inflammation, we show that sn-1,2-diacylglycerols block the cytokine storm, the expression of inflammatory mediators, and LPS-induced septic lung damage and mortality. sn-1,2-diacylglycerols reduce systemic inflammation by inhibiting LPS-induced p38 MAPK- and PI3K/AKT-mediated NF-κB activation in macrophages. These results suggest that exogenous DAG probably acts by blocking p38 MAPK or PI3K/AKT signal transduction, thereby down-regulating NF-κB activation and NF-κB-mediated transcription of genes encoding cytokines and pro-inflammatory oxidative enzymes. Our findings demonstrate that exogenous sn-1,2-diacylglycerol protects mice from LPS-induced lethal endotoxemia by suppressing TLR4-driven inflammatory responses, suggesting that 1,2-diacylglycerols may be used as dietary health supplements for the prevention or therapy of systemic inflammatory diseases.
    日期: 2016-11
    關聯: Immunobiology. 2016 Nov;221(11):1309-1318.
    Link to: http://dx.doi.org/10.1016/j.imbio.2016.05.007
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0171-2985&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000383823500010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84992451562
    顯示於類別:[郭呈欽] 期刊論文

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