化学
促炎细胞因子
邻苯二甲酸二丁酯
上睑下垂
组织蛋白酶B
脾脏
巨噬细胞极化
苯并(a)芘
体内
巨噬细胞
药理学
免疫学
炎症
致癌物
体外
生物化学
生物
炎症体
有机化学
受体
生物技术
酶
作者
Mingdan You,Yawen Song,Jing Chen,Yining Liu,Ganglong Yang,Yanli Cen,Xiaodeng Zhao,Zhongfa Tao,Guanghong Yang
标识
DOI:10.1016/j.scitotenv.2023.163460
摘要
Humans are often simultaneously exposed to benzo(a)pyrene (BaP) and dibutyl phthalate (DBP) through consumption of food and water. Yet, direct evidence of the link between BaP and DBP co-exposure and the risk of splenic injury is lacking. In the present study, we established the rats and primary splenic macrophages models to evaluate the effects of BaP or/and DBP exposure on spleen and underlying mechanisms. Compared to the single exposure or control groups, the co-exposure group showed more severe spleen damage and higher production of pro-inflammatory cytokines. Co-exposure to BaP and DBP resulted in a 1.79-fold, 2.11-fold and 1.9-fold increase in the M1 macrophage markers iNOS, NLRP3 (pyroptosis marker protein) and cathepsin B (CTSB), respectively, and a 0.8-fold decrease in the M2 macrophage marker Arg1 in vivo. The more prominent effects in perturbation of imbalance in M1/M2 polarization (iNOS, 2.25-fold; Arg1, 0.55-fold), pyroptosis (NLRP3, 1.43-fold), and excess CTSB (1.07-fold) in macrophages caused by BaP and DBP co-exposure in vitro were also found. Notably, MCC950 (the NLRP3-specific inhibitor) treatment attenuated the pro-inflammatory macrophage polarization and following pro-inflammatory cytokine production triggered by BaP and DBP co-exposure. Furthermore, CA-074Me (the CTSB-specific inhibitor) suppressed the macrophages pyroptosis, pro-inflammatory macrophage polarization, and secretion of pro-inflammatory cytokine induced by BaP and DBP co-exposure. In conclusion, this study indicates co-exposure to BaP and DBP poses a higher risk of spleen injury. Pro-inflammatory macrophage polarization regulated by pyroptosis involving CTSB underlies the spleen injury caused by BaP and DBP co-exposure.
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