Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
Int J Mol Sci. 2022 Aug 8;23(15):8826. doi: 10.3390/ijms23158826.
Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines as a late phase response. Attempts have been made to identify novel antiallergic compounds from natural materials such as Chinese medicines and food ingredients. We herein screened approximately 60 compounds and identified salicylaldehyde, an aromatic aldehyde isolated from plant essential oils, as an inhibitor of the IgE-mediated activation of MCs. A degranulation assay, flow cytometric analyses, and enzyme-linked immunosorbent assays revealed that salicylaldehyde inhibited the IgE-mediated degranulation and cytokine expression of bone-marrow-derived MCs (BMMCs). The salicylaldehyde treatment reduced the surface expression level of FcεRI, the high affinity receptor for IgE, on BMMCs, and suppressed the IgE-induced phosphorylation of tyrosine residues in intercellular proteins, possibly Lyn, Syk, and Fyn, in BMMCs. We also examined the effects of salicylaldehyde in vivo using passive anaphylaxis mouse models and found that salicylaldehyde administration significantly enhanced the recovery of a reduced body temperature due to systemic anaphylaxis and markedly suppressed ear swelling, footpad swelling, and vascular permeability in cutaneous anaphylaxis.
肥大细胞(MCs)在 IgE 介导的免疫反应中发挥关键作用,包括在寄生虫感染的保护以及过敏疾病的发作和/或症状中。IgE 介导的激活诱导 MC 释放介质,包括组胺和白三烯作为早期反应,并产生细胞因子作为晚期反应。已经尝试从天然材料(如中药和食品成分)中鉴定新型抗过敏化合物。我们在此筛选了大约 60 种化合物,并确定了水杨醛,一种从植物精油中分离出来的芳香醛,是 IgE 介导的 MC 激活的抑制剂。脱颗粒测定,流式细胞术分析和酶联免疫吸附测定显示,水杨醛抑制骨髓来源的 MC(BMMC)的 IgE 介导的脱颗粒和细胞因子表达。水杨醛处理降低了 BMMC 上 IgE 高亲和力受体 FcεRI 的表面表达水平,并抑制了 IgE 诱导的 BMMC 中细胞内蛋白质酪氨酸残基的磷酸化,可能是 Lyn、Syk 和 Fyn。我们还使用被动过敏小鼠模型检查了水杨醛的体内作用,发现水杨醛给药显著增强了因全身性过敏反应而降低的体温恢复,并显著抑制了皮肤过敏中的耳部肿胀、足垫肿胀和血管通透性。