HgCl2 exposure mediates pyroptosis of HD11 cells and promotes M1 polarization and the release of inflammatory factors through ROS/Nrf2/NLRP3

Abstract

Mercury (Hg) is a serious metal environmental pollutant. HgCl2 exposure causes pyroptosis. When macrophages are severely stimulated, they often undergo M1 polarization and release inflammatory factors. However, the mechanisms by which mercuric chloride exposure induces macrophage apoptosis, M1 polarization, and inflammatory factors remain unclear. HD11 cells were exposed to different concentrations of Hg chloride (180, 210 and 240 nM HgCl2). The results showed that mercury chloride exposure up-regulated ROS, C-Nrf2 and its downstream factors (NQO1 and HO-1), and down-regulated N-Nrf2. In addition, the expressions of focal death-related indicators (Caspase-1, NLRP3, GSDMD, etc.), M1 polarization marker CD86 and inflammatory factors (TNF-α, IL-1β) increased, and the above changes were related to mercury. Oxidative stress inhibitor (NAC) can block ROS/ NrF2-mediated oxidative stress, inhibit mercury-induced pyroptosis and M1 polarization, and effectively reduce the release of inflammatory factors. The addition of Vx-765 to inhibit pyroptosis can effectively alleviate M1 polarization of HD11 cells and reduce the expression of inflammatory factors. HgCl2 mediates pyroptosis of HD11 cells by regulating ROS/Nrf2/NLRP3, promoting M1 polarization and the release of inflammatory factors.

Keywords

• HgCl2
• Pyroptosis
• ROS/Nrf2/NLRP3 pathway
• M1 polarization
• Inflammatory factor