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

  • Front Pharmacol. 2019 Aug 2;10:869. doi: 10.3389/fphar.2019.00869.
Hima Dhakal  1  2 ,  Soyoung Lee  3 ,  Eun-Nam Kim  4 ,  Jin Kyeong Choi  5 ,  Min-Jong Kim  2 ,  Jinjoo Kang  2 ,  Young-Ae Choi  2 ,  Moon-Chang Baek  6 ,  Byungheon Lee  7 ,  Hyun-Shik Lee  8 ,  Tae-Yong Shin  9 ,  Gil-Saeng Jeong  4 ,  Sang-Hyun Kim  1  2
Affiliations
  • 1. Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea.
  • 2. Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea.
  • 3. Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, South Korea.
  • 4. College of Pharmacy, Keimyung University, Daegu, South Korea.
  • 5. Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.
  • 6. Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
  • 7. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, South Korea.
  • 8. School of Life Sciences, Kyungpook National University, Daegu, South Korea.
  • 9. College of Pharmacy, Woosuk University, Jeonju, South Korea.
PMID: 31427975 DOI: 10.3389/fphar.2019.00869
Abstract

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
Gomisin M2; allergic inflammation; anaphylaxis; calcium; mast cells.
Products