二嗪农是一种有机磷 (OP) 杀虫剂，在日本用于农业、家庭园艺和室内害虫防治。它可以激活巨噬细胞并诱导促炎反应，据报道会引起气道高反应性，这表明接触 OP 杀虫剂可能会导致哮喘恶化。尽管杀虫剂的使用与过敏性疾病的发病机制之间存在相关性，但目前还没有关于二嗪农对肥大细胞功能影响的报道。因此，在本研究中，我们研究了二嗪农对大鼠嗜碱性白血病（RBL）-2H3细胞肥大细胞功能的影响。令人惊讶的是，我们发现二嗪农抑制肥大细胞活化，尽管抑制程度随浓度而变化。二嗪农在 150μM 浓度下诱导活性氧 (ROS) 生成和 HO-1 表达，而不影响细胞活力。二嗪农抑制 RBL-2H3 细胞中 A23187 介导的脱颗粒以及 Tnf 和 Il4 表达，但不影响钙流入。当除去培养物上清液时，二嗪农对脱颗粒的抑制作用被逆转。作为钙内流下游的信号事件，二嗪农抑制 A23187 诱导的细胞外信号调节激酶 (ERK) 磷酸化，而 p38 磷酸化影响不大。二嗪农显着抑制 IgE 交联介导的脱颗粒以及 Tnf 和 IL4 表达的诱导，而二嗪农对钙内流影响很小。总之，二嗪农抑制肥大细胞活化，包括脱粒和细胞因子表达。在评估二嗪农的体内作用时，尽管二嗪农的作用因细胞类型而异，但应分别从基础和临床方面考虑其抑制肥大细胞活化的潜力，分别在过敏性疾病的病理生理学和发展中。 © 2024。由 Elsevier B.V. 出版

Diazinon is an organophosphorus (OP) insecticides used in agriculture, home gardening and indoor pest control in Japan. It can activate macrophages and induce pro-inflammatory responses and has been reported to cause airway hyper-reactivity, suggesting the possibility of asthma exacerbation from exposure to OP insecticides. Despite the correlation between insecticide use and the pathogenesis of allergic diseases, there have been no reports on the effects of diazinon on mast cell function. Therefore, in this study, we investigated the effects of diazinon on mast cell function in rat basophilic leukemia (RBL)-2H3 cells. Surprisingly, we found that diazinon inhibited mast cell activation, although the degree of inhibition varied with concentration. Diazinon induced reactive oxygen species (ROS) generation and HO-1 expression at a concentration of 150µM without affecting cell viability. Diazinon inhibited A23187-mediated degranulation and Tnf and Il4 expression in RBL-2H3 cells but did not affect calcium influx. Suppression of degranulation by diazinon was reversed when the culture supernatant was removed. As a signaling event downstream of calcium influx, diazinon inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) induced by A23187, whereas the phosphorylation of p38 had little effect. IgE cross-linking-mediated degranulation as well as the induction of Tnf and IL4 expression was significantly inhibited by diazinon, while diazinon had little effect on calcium influx. In conclusion, diazinon inhibited mast cell activation, including degranulation and cytokine expression. When evaluating the in vivo effects of diazinon, its potential to inhibit mast cell activation should be considered in the pathophysiology and development of allergic diseases in terms of basic and clinical aspects, respectively, although the effect of diazinon varies depending on the cell type.Copyright © 2024. Published by Elsevier B.V.