NLRP3 inflammasome-mediated endothelial cells pyroptosis is involved in decabromodiphenyl ethane-induced vascular endothelial injury.

Abstract:

:Decabromodiphenyl ethane (DBDPE) is a novel environmental pollutant that has attracted growing attention. Previous studies have indicated that DBDPE could induce vascular endothelial injury and cardiovascular damage, but the underlying mechanisms are not well understood. This study was designed to examine the mechanisms of DBDPE induces vascular endothelial injury. In vivo, Sprague-Dawley rats were administered with 0, 5, 50, 500 mg/kg bw/day of DBDPE via gavage for 28 days. Results showed that DBDPE could damage abdominal aortas morphological and ultrastructural structure and increase the protein levels of interleukin 1β (IL-1β) and interleukin 18 (IL-18) of the abdominal aortas. Moreover, DBDPE induced NLRP3 inflammasome activation and activated caspase-1 in abdominal aorta endothelium of rats. In vitro, human vascular endothelial cells (HAECs) were treated with different concentrations of DBDPE (0, 6.25, 12.5, 25, 50, and 100 μM). DBDPE not only induced cytotoxicity and reactive oxygen species (ROS) generation in HAECs but also caused HAECs pyroptosis, which was evidenced by the elevated expression of Nod-like receptor protein -3 (NLRP3), ASC, and caspase-1 in DBDPE-treated group. To further elucidate the effects of NLRP3 inflammasome on DBDPE-induced HAECs pyroptosis, we constructed NLRP3 knockdown HAECs by lentivirus-mediated short hairpin RNA (shRNA). And the results showed that NLRP3 knockdown downregulated DBDPE-induced increases of caspase-1 activity and caspase-1, ASC and NLRP3 mRNA and protein expression levels. Accordingly, our data suggested that DBDPE may damage vascular endothelium by NLRP3 inflammasome-mediated endothelial cells pyroptosis.

journal_name

Chemosphere

journal_title

Chemosphere

authors

Zheng D,Shi Z,Yang M,Liang B,Zhou X,Jing L,Sun Z

doi

10.1016/j.chemosphere.2020.128867

subject

Has Abstract

pub_date

2021-03-01 00:00:00

pages

128867

eissn

0045-6535

issn

1879-1298

pii

S0045-6535(20)33065-4

journal_volume

267

pub_type

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