國家衛生研究院 NHRI:Item 3990099045/7665
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    題名: A tryptophan metabolite, kynurenine, promotes mast cell activation through Aryl hydrocarbon receptor
    作者: Kawasaki, H;Chang, HW;Tseng, HC;Hsu, SC;Yang, SJ;Hung, CH;Zhou, Y;Huang, SK
    貢獻者: Division of Environmental Health and Occupational Medicine
    摘要: Background:Aryl hydrocarbon receptor (AhR; a unique cellular chemical sensor) has been recognized as a receptor for many of the common environmental contaminants, dietary and endogenous metabolites, and capable of regulating immune responses. Recently, tryptophan metabolites have been suggested to play a role in immune modulation, some of which have been suggested to be AhR ligands. But, their involvement in modulating the functions of mast cell, a critical cell type in innate immunity and allergic diseases, remains to be fully defined. We therefore investigated the functional impacts of tryptophan metabolites on human and mouse mast cell responses in vitro and their functional importance in vivo. Methods: Three tryptophan metabolites, kynurenine (KYN), kynurenic acid (KA) and quinolinic acid (QA), were examined in terms of their effect on IgE-mediated responses in mouse bone marrow-derived mast cells (BMMCs), in vivo anaphylactic responses and in human peripheral blood-derived cultured mast cells (HCMCs). For evaluation of AhR involvement, we examined the responses of mast cells from AhR-null or -wild type mice with the use of a known AhR antagonist, CH223191. Results: KYN, but not KA and QA, enhanced IgE-mediated responses, including degranulation, LTC4 release and IL-13 production in BMMCs through the activation of PLC c1, Akt, MAPK p38, and the increase of intracellular calcium. KYN also enhanced cutaneous anaphylaxis in vivo. These enhancing effects of KYN were not observed in AhR-deficient MMCs and could be inhibited by CH223191 in BMMCs. Furthermore, KYN had similar enhancing effects on HCMCs, which were inhibited by CH223191. Conclusion(s): The AhR-KYN axis is potentially important in modulating mast cell responses, and represents an example of AhR’s critical involvement in the regulation of allergic responses.
    日期: 2013-11
    關聯: Allergy. 2013 Nov;68(Suppl. S98):6.
    Link to: http://dx.doi.org/10.1111/all.12281
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0105-4538&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000325897100019
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