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.

Highlights

  • Mast cells are primary immune cells with pivotal roles in allergic inflammatory reactions (Wernersson and Pejler, 2014)

  • To determine the anti-allergic effects of G.M2, we performed a degranulation assay based on the release of histamine and β-hexosaminidase in Mouse bone marrow–derived mast cells (mBMMCs)

  • We used various types of murine mast cells to evaluate the antiallergic effect of G.M2, though mBMMCs were predominant cells used in our study

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Summary

Introduction

Mast cells are primary immune cells with pivotal roles in allergic inflammatory reactions (Wernersson and Pejler, 2014). Mast cells secrete a wide range of biological mediators, which collectively account for the pathology of allergic inflammation (Theoharides et al, 2012) These include preformed secretory granules (containing histamine and proteases) as well as cytokines, chemokines, and growth factors, which are synthesized upon mast cell activation (Espinosa and Valitutti, 2018). FcεRI-mediated signaling activates another PTK, Fyn, which enhances Syk activation This is followed by activation of Grb2-associated binding protein 2 and phosphoinositide 3-kinase (PI3K) (Gilfillan and Tkaczyk, 2006). Both PTKs are important for activation of various signaling pathways, including the PI3K, phospholipase C (PLC)γ, Akt, and nuclear factor (NF)-κB pathways. These signaling events lead to the initiation of inflammatory responses via intracellular calcium release, degranulation, and cytokine secretion (Siraganian et al, 2010)

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