PMID- 31427975 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 10 DP - 2019 TI - Gomisin M2 Inhibits Mast Cell-Mediated Allergic Inflammation via Attenuation of FcepsilonRI-Mediated Lyn and Fyn Activation and Intracellular Calcium Levels. PG - 869 LID - 10.3389/fphar.2019.00869 [doi] LID - 869 AB - Mast cells are effector cells that induce allergic inflammation by secreting inflammatory mediators. Gomisin M2 (G.M2) is a lignan isolated from Schisandra chinensis (Turcz). Baill. exhibiting anti-cancer activities. We aimed to investigate the anti-allergic effects and the underlying mechanism of G.M2 in mast cell-mediated allergic inflammation. For the in vitro study, we used mouse bone marrow-derived mast cells, RBL-2H3, and rat peritoneal mast cells. G.M2 inhibited mast cell degranulation upon immunoglobulin E (IgE) stimulation by suppressing the intracellular calcium. In addition, G.M2 inhibited the secretion of pro-inflammatory cytokines. These inhibitory effects were dependent on the suppression of FcepsilonRI-mediated activation of signaling molecules. To confirm the anti-allergic effects of G.M2 in vivo, IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were utilized. Oral administration of G.M2 suppressed the PCA reactions in a dose-dependent manner. In addition, G.M2 reduced the ASA reactions, including hypothermia, histamine, interleukin-4, and IgE production. In conclusion, G.M2 exhibits anti-allergic effects through suppression of the Lyn and Fyn pathways in mast cells. According to these findings, we suggest that G.M2 has potential as a therapeutic agent for the treatment of allergic inflammatory diseases via suppression of mast cell activation. FAU - Dhakal, Hima AU - Dhakal H AD - Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea. AD - Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Lee, Soyoung AU - Lee S AD - Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, South Korea. FAU - Kim, Eun-Nam AU - Kim EN AD - College of Pharmacy, Keimyung University, Daegu, South Korea. FAU - Choi, Jin Kyeong AU - Choi JK AD - Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, United States. FAU - Kim, Min-Jong AU - Kim MJ AD - Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Kang, Jinjoo AU - Kang J AD - Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Choi, Young-Ae AU - Choi YA AD - Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Baek, Moon-Chang AU - Baek MC AD - Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Lee, Byungheon AU - Lee B AD - Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, South Korea. FAU - Lee, Hyun-Shik AU - Lee HS AD - School of Life Sciences, Kyungpook National University, Daegu, South Korea. FAU - Shin, Tae-Yong AU - Shin TY AD - College of Pharmacy, Woosuk University, Jeonju, South Korea. FAU - Jeong, Gil-Saeng AU - Jeong GS AD - College of Pharmacy, Keimyung University, Daegu, South Korea. FAU - Kim, Sang-Hyun AU - Kim SH AD - Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea. AD - Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea. LA - eng PT - Journal Article DEP - 20190802 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6688163 OTO - NOTNLM OT - Gomisin M2 OT - allergic inflammation OT - anaphylaxis OT - calcium OT - mast cells EDAT- 2019/08/21 06:00 MHDA- 2019/08/21 06:01 PMCR- 2019/08/02 CRDT- 2019/08/21 06:00 PHST- 2019/03/24 00:00 [received] PHST- 2019/07/08 00:00 [accepted] PHST- 2019/08/21 06:00 [entrez] PHST- 2019/08/21 06:00 [pubmed] PHST- 2019/08/21 06:01 [medline] PHST- 2019/08/02 00:00 [pmc-release] AID - 10.3389/fphar.2019.00869 [doi] PST - epublish SO - Front Pharmacol. 2019 Aug 2;10:869. doi: 10.3389/fphar.2019.00869. eCollection 2019.