Glycogen synthase kinase 3β inhibition prevents monocyte migration across brain endothelial cells via Rac1-GTPase suppression and down-regulation of active integrin conformation.

ABSTRACT: Glycogen synthase kinase (GSK) 3β has been identified as a regulator of immune responses. We demonstrated previously that GSK3β inhibition in human brain microvascular endothelial cells (BMVECs) reduced monocyte adhesion/migration across BMVEC monolayers. Herein, we tested the idea that GSK3β inhibition in monocytes can diminish their ability to engage the brain endothelium and migrate across the blood-brain barrier. Pretreatment of primary monocytes with GSK3β inhibitors resulted in a decrease in adhesion (60%) and migration (85%), with similar results in U937 monocytic cells. Monocyte-BMVEC interactions resulted in diminished barrier integrity that was reversed by GSK3β suppression in monocytic cells. Because integrins mediate monocyte rolling/adhesion, we detected the active conformatio

SUBMITTER: Rom S 

PROVIDER: S-EPMC3463628 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature