國家衛生研究院 NHRI:Item 3990099045/6454
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    題名: Role of the Aryl-hydrocarbon Receptor (AhR)-ligand axis in mast cells
    作者: Zhou, Y;Tung, H;Tsai, Y;Hsu, S;Plunkett, B;Vonakis, BM;Huang, S
    貢獻者: Division of Environmental Health and Occupational Medicine
    摘要: RATIONALE: The significance of AhR signaling in immune regulation has been suggested, but its role in mast cells remains unknown. We hypothesized that AhR and its ligands may affect mast cells function and play an important role in the regulation of allergic diseases. METHODS: Mouse bone marrow-derived mast cells (BMMCs) were treated with several known AhR ligands including TCDD and FICZ. The levels of cytokines and mediators release in activated mast cells by IgE/Ag cross-linkage were analyzed. The in vivo effect was tested by passive cutaneous anaphylaxis (PCA). Reactive oxygen species (ROS) and intra-cellular calcium were detected by Flow cytometry. ERK and PKC phosphorylation was detected by Western blotting. RESULTS: Exposure of BMMCs to low-doses ( < 10 nM) of AhR ligands significantly increased the levels of IL-13, degranulation, LTC 4 , and PCA response. Mechanistically, exposure of the cells to AhR ligands resulted in significantly increased levels of intracellular calcium and ROS, concomi-tant with enhanced activation of several signaling pathways involving ERK and PKC. Notably, the functional effects of AhR ligands could be re-versed by the addition of an antioxidant, N-acetylcysteine, and calcium channel blockers. In addition, when BMMCs from AhR-null mice were an-alyzed, significant reductions in the numbers of BMMCs and in the levels of IL-3-induced proliferation were noted, as compared to those seen in wild-type mice. Mast cell deficiency was confirmed in various tissues and peritoneal cavity of AhR-null mice. CONCLUSIONS: These results thus provide evidence supporting critical roles of AhR signaling in maintaining the homeostasis, maturation and optimal activation of mast cells.
    日期: 2012-02
    關聯: Journal of Allergy and Clinical Immunology. 2012 Feb;129(2 Suppl):AB121.
    Link to: http://dx.doi.org/10.1016/j.jaci.2011.12.581
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0091-6749&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000301133400458
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