Metformin inhibits IgE- and aryl hydrocarbon receptor-mediated mast cell activation in vitro and in vivo

European Journal of Immunology
Hsueh-Chun Wang, Shau-Ku Huang

Abstract

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 FcεR1-, AhR-mediated signaling or their combination. Metformin at relatively low doses was shown to suppress FcεR1-mediated degranulation, IL-13, TNF-α 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 FcεR1- 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 lya...Continue Reading

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Citations

Oct 11, 2019·International Journal of Molecular Sciences·Misun KimDooil Jeoung
Aug 21, 2019·Journal of Translational Medicine·Yi-Bo HouJia-Jie Chen
Dec 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shu-Lan QuYi-Fu Yang
Apr 21, 2020·International Immunopharmacology·Yi-Bo HouJia-Jie Chen
Feb 2, 2021·The Lancet. Healthy Longevity·Carolyn T BramanteChristopher J Tignanelli
Mar 3, 2020·The Science of the Total Environment·Esmeralda Michelle Sánchez-OcampoLeobardo Manuel Gómez-Oliván
Jun 18, 2021·Frontiers in Immunology·Misun KimDooil Jeoung
Aug 10, 2021·Frontiers in Endocrinology·Sherehan IbrahimNicholas Ingraham
Feb 26, 2020·Journal of Agricultural and Food Chemistry·Chongyang WangGuanghai Yan

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