國家衛生研究院 NHRI:Item 3990099045/11437
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    題名: Metformin inhibits IgE- and aryl hydrocarbon receptor-mediated mast cell activation in vitro and in vivo
    作者: Wang, HC;Huang, SK
    貢獻者: National Institute of Environmental Health Sciences
    摘要: Metformin, an anti-diabetic drug, possesses anti-inflammatory property beyond its glucose-lowering activity, but its regulatory effect on mast cells and allergic responses remains unknown, wherein the aryl hydrocarbon receptor (AhR)-ligand axis is critical in controlling mast cell activation. Herein, we provide evidence supporting the role of metformin in modulating mast cell activation by FcepsilonR1-, AhR-mediated signaling or their combination. Metformin at relatively low doses was shown to suppress FcepsilonR1-mediated degranulation, IL-13, TNF-alpha and sphingosine-1-phosphate (S1P) secretion in murine bone marrow-derived mast cells (BMMCs). In contrast, metformin at the same doses potently inhibited all parameters in mast cells stimulated with an AhR ligand, 5,11-dihydroindolo[3,2-b]carbazole-6-carbaldehyde (FICZ). Further, metformin was shown to inhibit FcepsilonR1- and AhR-mediated passive cutaneous anaphylaxis (PCA) in vivo, reversible by a S1P receptor 2 antagonist, JTE-013. Using AhR reporter cells, Huh7-DRE-Luc cells, a human mast cell line, HMC-1, and BMMCs, metformin's inhibitory effect was mediated through the suppression of FICZ-induced AhR activity, calcium mobilization and ROS generation. Notably, FICZ-mediated oxidation of S1P lyase (S1PL) and its reduced activity were reversed by metformin, resulting in decreased levels of S1P. Collectively, these results suggested the potential utility of metformin in treating allergic diseases, particularly in cases with comorbid type II diabetes mellitus. This article is protected by copyright. All rights reserved.
    日期: 2018-09-22
    關聯: European Journal of Immunology. 2018 Dec;48 (12):1989-1996.
    Link to: http://dx.doi.org/10.1002/eji.201847706
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000452047500008
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85055543588
    顯示於類別:[黃嘯谷] 期刊論文

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