Ogasawara Nanako, Matsushima Miyoko, Kawamura Nami, Atsumi Kazuko, Yamaguchi Takehiro, Ochi Haruka, Kusatsugu Yuto, Oyabu Sayaka, Hashimoto Naozumi, Hasegawa Yoshinori, Ueyama Jun, Kawabe Tsutomu
Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daikou-minami, Higashi-ku, Nagoya, 461-8673, Japan.
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Toxicology. 2017 Mar 15;379:22-30. doi: 10.1016/j.tox.2017.01.014. Epub 2017 Jan 21.
Diazinon is an organophosphorus (OP) insecticide and is widely used not only in agriculture but also homes and garden in Japan. Diazinon has been reported to increase TNF-α production in rat serum and brain, suggesting that it can modify the proinflammatory response. In this study, we investigated the effects of diazinon on macrophage functions, such as cytokine production, reactive oxygen species (ROS) generation, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions, cell-surface molecule expressions, and phagocytosis in RAW264.7 cells. In RAW264.7 cells, diazinon induced the production of TNF-α and IL-6. Diazinon induced ROS generation and the expressions of COX-2, iNOS, and cell-surface molecules CD40, CD86, and MHC class II, but reduced phagocytic activity in RAW264.7 cells. ERK and p38, but not JNK and p65 were involved in diazinon-induced IL-6 expression in RAW264.7 cells. We also examined these proinflammatory responses in bone marrow-derived macrophages (BMDM) and bronchoalveolar lavage fluid (BALF) cells. These results suggested that diazinon can activate macrophages and enhance inflammatory responses.
二嗪农是一种有机磷杀虫剂，在日本不仅广泛用于农业，还用于家庭和花园。据报道，二嗪农可增加大鼠血清和脑中肿瘤坏死因子-α（TNF-α）的产生，这表明它可以改变促炎反应。在本研究中，我们研究了二嗪农对巨噬细胞功能的影响，如细胞因子产生、活性氧（ROS）生成、环氧化酶（COX）-2和诱导型一氧化氮合酶（iNOS）表达、细胞表面分子表达以及RAW264.7细胞中的吞噬作用。在RAW264.7细胞中，二嗪农诱导TNF-α和白细胞介素-6（IL-6）的产生。二嗪农诱导RAW264.7细胞中ROS生成以及COX-2、iNOS和细胞表面分子CD40、CD86和II类主要组织相容性复合体（MHC）的表达，但降低了RAW264.7细胞的吞噬活性。细胞外信号调节激酶（ERK）和p38，而非应激活化蛋白激酶（JNK）和核因子κB（p65）参与了二嗪农诱导的RAW264.7细胞中IL-6的表达。我们还检测了骨髓来源的巨噬细胞（BMDM）和支气管肺泡灌洗液（BALF）细胞中的这些促炎反应。这些结果表明，二嗪农可激活巨噬细胞并增强炎症反应。
