Abstract
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 and ICAM-1 in bEnd.3 mouse brain endothelial cells (EC). Cd stimulated PGE2 release in a time and dose dependent manner, which was accompanied by increase of COX-2 expression. The thiol-reducing antioxidant N-acetylcyteine attenuated Cd-induced PGE2 production and COX-2 expression. Cd increased phosphorylation of p38 MAPK, but not of JNK and ERK1/2. A blockade of p38 MAPK pathway abrogated Cd-induced COX-2 expression and PGE2 production. Cd-induced ICAM-1 expression and leukocyte-EC adhesion were diminished by non-steroidal anti-inflammatory drugs such as indomethacin and NS-398, which was reversed by addition of PGE2. Together, these data suggest that Cd induces COX-2 expression through the activation of p38 MAPK, an oxidative stress-sensitive cellular signaling molecule, and induction of COX-2 is associated with ICAM-1 expression in brain endothelial cells following Cd exposure.
Original language | English (US) |
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Pages (from-to) | 212-220 |
Number of pages | 9 |
Journal | Toxicology Letters |
Volume | 165 |
Issue number | 3 |
DOIs | |
State | Published - Sep 10 2006 |
Externally published | Yes |
Keywords
- Brain endothelial cells
- Cadmium
- Cyclooxygenase-2
- ICAM-1
ASJC Scopus subject areas
- Toxicology