U0126, MEK1/2 inhibitor, Induces Adhesion Molecules Expression in Human Blood Cells

B₂-Integrin (CD11b) and L-selectin (CD62L) adhesion molecule play crucial roles in monocyte transmigration and adherence to endothelial cells, causing inflammatory responses in vascular lesion. MAPKinase pathway has been known to be activated in inflammatory responses. In this study, we investigated the expression of adhesion molecule by MEK1/2 inhibotors such as U0126 in human blood cells, U937 cells. Cell viability was determined by MTT assay. The expression of adhesion molecule was observed by flow cytometry. Adhesion molecules were time- and dose-dependently incresed by U0126. U0126 decreased ERK activity in a concentration-dependent manner. To investigate the mechanism of U0126-induced adhesion molecules, we examined the effects of various inhibitors such as LY294002 (an inhibitor for PI3Kinase), trolox (antioxidant), rottlerin (an inhibitor for PKC-δ), and SN50 (an inhibitor for NF-kB) on U0126-induced adhesion molecule expression. Adhesion molecule expression was attenuated by rottlerin and trolox. In addition, to examine cell type specificity of U0126 effect on adhesion molecule, we investigated ICAM-1 expression in other cells including human T cells, brain endothelial cells and fibroblast cells. In bEnd.3 cells and NIH3T3 cells, U0126 had no effect on ICAM-1 expression. These results indicate that expression of adhesion molecule was increased by MEK1/2 inhibotors, such as U0126, in human blood cells and the expression of adhesion molecules may involve the downregulation of ERK MAPK pathway.

Author dc:creator

• 박, 성례

Contributors dc:contributor

• 문, 창현
• 대학원 의학과
• 200324263

• U0126
• 혈액세포
• 부착분자
• ERK
• human blood cell
• adhesion molecule

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000364
000000000364

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1490