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
References
Oct 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hans M RosenfeldtSarah Spiegel
May 23, 2006·Journal of Hazardous Materials·How-Ran ChaoWen-Jhy Lee
Jan 10, 2009·Science·Joanna WegrzynAndrew C Larner
Jun 19, 2010·The Journal of Biological Chemistry·Darci PhillipsRobert S Balaban
Jun 30, 2011·Advances in Experimental Medicine and Biology·Ana Olivera, Juan Rivera
Mar 7, 2013·Blood·Yufeng ZhouShau-Ku Huang
Apr 13, 2013·International Immunology·Nam Trung NguyenTadamitsu Kishimoto
Aug 22, 2013·Seminars in Immunopathology·Celine A Beamer, David M Shepherd
Mar 25, 2014·Molecular Immunology·Riccardo SibilanoGiorgia Gri
Jun 6, 2014·Nature·Michael Maceyka, Sarah Spiegel
Jun 15, 2014·The Journal of Biological Chemistry·Jia CaoLing He
Aug 12, 2014·Toxicology and Applied Pharmacology·Minh Truong DoHye Gwang Jeong
Dec 17, 2014·The Journal of Allergy and Clinical Immunology·Carole A OskeritzianSarah Spiegel
Feb 5, 2015·Cell Metabolism·Ling He, Fredric E Wondisford
Feb 24, 2015·Toxicology and Applied Pharmacology·Zaid H MaayahHesham M Korashy
Mar 17, 2015·Endocrine, Metabolic & Immune Disorders Drug Targets·Yoshifumi Saisho
Mar 29, 2016·International Journal of Biological Sciences·Rui Yang, Mercedes Rincon
Jun 2, 2016·Respirology : Official Journal of the Asian Pacific Society of Respirology·Chun-Yi LiChung-Hsuen Wu
Jul 16, 2016·Circulation Research·Amy R CameronGraham Rena
Oct 7, 2016·Archives of Toxicology·Hsueh-Chun WangShau-Ku Huang
Mar 30, 2017·Frontiers in Immunology·Sabira Mohammed, K B Harikumar
Mar 20, 2018·International Journal of Chronic Obstructive Pulmonary Disease·Raju BishwakarmaGulshan Sharma
Mar 27, 2018·Forensic Science International : Synergy·C HessD Tschoepe
May 18, 2018·Cellular & Molecular Immunology·Hsueh-Chun WangShau-Ku Huang
Jul 17, 2018·Cell·Yoku Hayakawa, Timothy C Wang
Citations
Oct 11, 2019·International Journal of Molecular Sciences·Misun KimDooil Jeoung
Aug 21, 2019·Journal of Translational Medicine·Yi-Bo HouJia-Jie Chen
Aug 25, 2020·Canadian Respiratory Journal : Journal of the Canadian Thoracic Society·Li WenChen Yunzhi
Dec 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shu-Lan QuYi-Fu Yang
Jan 29, 2021·Immunopharmacology and Immunotoxicology·Nageh Ahmed El-MahdySally El-Sayed Abu-Risha
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
Sep 29, 2021·Chinese Medicine·Lin HanXiao-Lin Tong