Cadmium mediates pyroptosis of human dermal lymphatic endothelial cells in a NLRP3 inflammasome-dependent manner.

Abstract

Pyroptosis is a form of inflammasome-trigged programmed cell death in response to a variety of stimulators, including environmental cytotoxic pollutant Cadmium (Cd). Vascular endothelial cell is one of the first-line cell types of Cd cell toxicity. Studies report that Cd exposure causes pyroptosis in vascular endothelial cells. Vascular and lymphatic endothelial cells have many common properties, but these two cell types are distinguished in gene expression profile and the responsive behaviors to chemokine or physical stimulations. Whether Cd exposure also causes pyroptosis in lymphatic endothelial cells has not been investigated. Here, we found that Cd treatment significantly decreased the viability of human dermal lymphatic endothelial cells (HDLECs). Cd treatment induced inflammasome activation indicated by elevated cleavage of pro-caspase-1 into active form Casp1p20, elevated secretion of pro-inflammatory cytokines and production of reactive oxygen species (ROS). Flow cytometry showed that caspase-1 activity was significantly increased in Cd-treated cells. Moreover, knockdown of NLRP3 effectively rescued Cd-induced inflammasome activation and pyroptosis in HDLECs. Collectively, our results indicated that Cd induced pyroptosis in a NLRP3 inflammasome-dependent manner in lymphatic endothelial cells.