Cadmium stimulates the expression of ICAM-1 via NF-κB activation in cerebrovascular endothelial cells

Abstract

Cadmium (Cd), a ubiquitous heavy metal, has been shown to accumulate in the central nervous system, especially outside of the blood–brain barrier (BBB), suggesting a potential toxicity to nervous tissue. Thus, we investigated the effect of Cd on intercellular adhesion molecule-1 (ICAM-1) expression, as an indicator of BBB injury, in mouse brain microvessel endothelial cells (bEnd.3 cells). The treatment with Cd increased the expression of ICAM-1 at the levels of protein and mRNA, and these increases were almost completely inhibited by a specific NF-κB inhibitor SN50. The treatment with Cd induced the translocation of NF-κB from cytosolic to membrane fraction and increased DNA binding activity of NF-κB, and this NF-κB activation was inhibited by SN50. Interestingly, Cd did not trigger the degradation of IκBα, suggesting that Cd-induced ICAM-1 expression is mediated through IκBα degradation-independent pathway. Instead, tyrosine phosphorylation of IκBα was significantly elevated by Cd treatment, and this elevation was blocked by genistein, a protein tyrosine kinase inhibitor. In summary, the present results suggest that Cd stimulates the expression of ICAM-1 in bEnd.3 cells, via NF-κB activation that is mediated by the tyrosine phosphorylation of IκBα.