Imidacloprid activates Kupffer cells pyroptosis to induce liver injury in mice via P2X7.

Abstract

This work aimed to investigate the mechanism by which the environmental poison imidacloprid (IMI) induced liver injury. First of all, IMI at the ED50=100μM was added to treat mouse liver Kupffer cells, thereafter, the occurrence of pyroptosis was detected by flow cytometry (FCM), transmission electron microscope (TEM), immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), RT-QPCT and Western-Blot (WB) assay. Furthermore, P2X7 expression was knocked out in Kupffer cells, and cells were treated with the P2X7 inhibitor, so as to observe the pyroptosis level induced by IMI after P2X7 suppression. In animal experiments, IMI was used to induce mouse liver injury, then the P2X7 inhibitor and pyroptosis inhibitor were added to treat the mice, respectively, so as to observe the effect on liver injury. IMI induced Kupffer cell pyroptosis, P2X7 knockout or P2X7 inhibitor treatment suppressed the effect of IMI and reduced the pyroptosis level. In animal experiments, the application of both P2X7 inhibitor and pyroptosis inhibitor decreased the cell injury level. IMI induces Kupffer cell pyroptosis via P2X7 and induce liver injury, and inhibiting the occurrence of pyroptosis can suppress the hepatotoxicity of IMI.