1. Academic Validation
  2. Combined exposure to benzo(a)pyrene and dibutyl phthalate aggravates pro-inflammatory macrophage polarization in spleen via pyroptosis involving cathepsin B

Combined exposure to benzo(a)pyrene and dibutyl phthalate aggravates pro-inflammatory macrophage polarization in spleen via pyroptosis involving cathepsin B

  • Sci Total Environ. 2023 Apr 13;163460. doi: 10.1016/j.scitotenv.2023.163460.
Mingdan You 1 Yawen Song 1 Jing Chen 1 Yining Liu 1 Wenyan Chen 1 Yanli Cen 1 Xiaodeng Zhao 2 Zhongfa Tao 2 Ganghong Yang 3
Affiliations

Affiliations

  • 1 School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, China.
  • 2 Guizhou Center for Disease Control and Prevention, Guiyang, Guizhou 550004, China.
  • 3 Guizhou Center for Disease Control and Prevention, Guiyang, Guizhou 550004, China; School of Public Health, Guizhou Medical University, Guiyang 550025, China. Electronic address: ghyang_gzmu@outlook.com.
Abstract

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.

Keywords

Benzo(a)pyrene; Cathepsin B; Dibutyl phthalate; Macrophages polarization; Pyroptosis; Spleen.

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