Cadmium exposure induces interleukin-6 production via ROS-dependent activation of the ERK1/2 but independent of JNK signaling pathway in human placental JEG-3 trophoblast cells

Abstract

Maternal exposure to cadmium (Cd) has been associated with preeclampsia (PE), which is a multisystemic disorder characterized by endothelial dysfunction. Elevated interleukin (IL)-6 expression is linked to PE and has been suggested to contribute to maternal endothelial dysfunction. Cd induces IL-6 production in various cell types through different signaling pathways. Thus, this study was designed to investigate the effect of Cd on IL-6 production and the underlying mechanisms in a trophoblast-derived cell line. Cultured JEG-3 trophoblast cells were exposed to non-toxic concentrations of CdCl2 in the presence or absence of various MAPK inhibitors or N-Acetyl-L-cysteine (NAC). IL-6 was measured by ELISA. Phosphorylation of ERK1/2, JNK, and c-Jun was assessed by Western blotting. Cd exposure induced IL-6 production and increased ERK1/2, JNK, and c-Jun phosphorylation. NAC and the inhibition of ERK1/2 significantly reduced Cd-induced IL-6 production. These data indicate that Cd induces IL-6 production in trophoblast cells through a ROS-dependent activation of ERK1/2.