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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00869

Gomisin M2 Inhibits Mast Cell-Mediated Allergic Inflammation via Attenuation of FcεRI-Mediated Lyn and Fyn Activation and Intracellular Calcium Levels

Hima Dhakal1, Soyoung Lee2, Eun-Nam Kim3, Jin Kyeong Choi4,  Min-Jong Kim1, Jinjoo Kang1, Young-Ae Choi1, Moon-Chang Baek1, Byungheon Lee1, Hyun-Shik Lee1, Tae-Yong Shin5, Gil-Saeng Jeong3 and  Sang-Hyun Kim6*
  • 1Kyungpook National University, South Korea
  • 2Korea Research Institute of Bioscience and Biotechnology, South Korea
  • 3Keimyung University, South Korea
  • 4National Institutes of Health, United States
  • 5Woosuk University, South Korea
  • 6School of Medicine, Kyungpook National University, South Korea

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 FcεRI-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.

Keywords: Mast Cells, allergic inflammation, Anaphylaxis, Gomisin M2, Calcium

Received: 24 Mar 2019; Accepted: 08 Jul 2019.

Edited by:

Vincent Kam Wai Wong, Macau University of Science and Technology, Macau

Reviewed by:

Marselina I. Tan, Bandung Institute of Technology, Indonesia
Ivo R. De Seabra Rodrigues Dias, Macau University of Science and Technology, Macau  

Copyright: © 2019 Dhakal, Lee, Kim, Choi, Kim, Kang, Choi, Baek, Lee, Lee, Shin, Jeong and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sang-Hyun Kim, School of Medicine, Kyungpook National University, Daegu, South Korea, shkim72@knu.ac.kr