COX-2 is associated with cadmium-induced ICAM-1 expression in cerebrovascular endothelial cells.
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 PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE(2). 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.
Seok
Sun Mi
SM
Department of Physiology, School of Medicine, Ajou University, Suwon 443-749, South Korea.
Park
Dong Hyun
DH
Kim
Young-Chae
YC
Moon
Chang-Hyun
CH
Jung
Yi-Sook
YS
Baik
Eun Joo
EJ
Moon
Chang-Kiu
CK
Lee
Soo Hwan
SH
D000818:Animals; D001921:Brain / Q000098:blood supply; D002104:Cadmium / Q000633:toxicity*; D002448:Cell Adhesion / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002104:Cadmium; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone