In order to get insight into the mechanism of cadmium (Cd)-induced brain injury, we investigated the effects of Cd on the induction of COX-2 in bEnd.3 mouse brain endothelial cells. Cd induced COX-2 expression and PGE₂ release, which were attenuated by thiol-reducing antioxidant N-acetylcysteine (NAC) indicating oxidative components might contribute to these events. Indeed, Cd increased cellular reactive oxygen species (ROS) level and DNA binding activity of nuclear factor-kB (NF-κB), an oxidative stress sensitive transcription factor. Cd-induced PGE₂ production and COX-2 expression were significantly attenuated by Bay 11 7082, a specific inhibitor of NF-κB and by SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK). These data suggest that Cd induces COX-2 expression through activation of NF-κB and p38 MAPK, the oxidative stress-sensitive signaling molecules, in brain endothelial cells.
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