Cyclooxygenase-2 is Associated with Cadmium-induced ICAM-1 Expression in Brain Endothelial Cell

Exposure to cadmium (Cd) was reported to be related with the increased incidence of neurodegenerative diseases including stroke, though underlying mechanism is not clearly understood. In vivo studies showed that Cd accumulates out-side of blood brain barrier (BBB) and induces the leakage of BBB, suggesting brain endothelium as a putative target. Recently, we have reported that Cd stimulates ICAM-1 expression via NF-kB activation in bEnd.3 cerebrovascular endothelial cells. And also, we observed Cd induces cyclooxygenase-2 (COX-2) expression, and thereby prostaglandin E2 (PGE₂) production in bEnd.3. Based on the previous report that PGE₂ is one of the key regulators in the expression of cell adhesion molecule, in this study, we explored the possible role of COX-2 in Cd-induced ICAM-1 expression in bEnd.3. Cd upregulated ICAM-1 at the levels of mRNA and protein, but downregulated E-cadherin expression in bEnd.3. Other adhesion molecules such as VCAM-1 and VE-cadherin were not affected by Cd treatment. Cd-induced ICAM-1 expression was attenuated by COX-2 inhibitors, and effects of COX-2 inhibitors were blocked by exogenous PGE₂. COX-2 inhibitors recovered E-cadherin expression in bEnd.3 exposed to Cd. Cd increased leucocyte-adhesion to endothelial cells, which was mitigated by COX-2 inhibitors. These data strongly suggest that COX-2 is associated with Cd-induced ICAM-1 expression in bEnd.3. Pro-inflammatory cytokines such as TNFα and IL-1β increased ICAM-1 and COX-2 expression in bEnd.3, but COX-2 inhibitors minimally affected ICAM-1 expression, suggesting above results might be specific to Cd.

Author dc:creator

• 석, 선미

Contributors dc:contributor

• 이, 수환
• 대학원 의학과
• 200324269

• Cadmium (Cd)
• Cyclooxygenase (COX-2)
• Prostaglandin
• E₂(PGE₂)
• Intercellular adhesion molecule (ICAM-1)
• Brain microvascular endothelial cell(bEnd.3)

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000192
000000000192

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1485