ArticleThe American journal of pathology2012
Glycogen synthase kinase 3β inhibition prevents monocyte migration across brain endothelial cells via Rac1-GTPase suppression and down-regulation of active integrin conformation.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
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- Glycogen synthase kinase-3: the master switch driving neurodegeneration in Alzheimer's disease and Parkinson's disease.Archives of toxicology · 2025Review
- Direct Current Electric Field Coordinates the Migration of BV2 Microglia via ERK/GSK3β/Cofilin Signaling Pathway.Molecular neurobiology · 2022Article
- Lithium causes differential effects on postsynaptic stability in normal and denervated neuromuscular synapses.Scientific reports · 2021Article
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- Macrophage Function and the Role of GSK3.International journal of molecular sciences · 2021Review
- miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.American journal of physiology. Cell physiology · 2020Article
- let-7g counteracts endothelial dysfunction and ameliorating neurological functions in mouse ischemia/reperfusion stroke model.Brain, behavior, and immunity · 2020Article
- Combination of HIV-1 and Diabetes Enhances Blood Brain Barrier Injury via Effects on Brain Endothelium and Pericytes.International journal of molecular sciences · 2020Article
- Hyperglycemia and advanced glycation end products disrupt BBB and promote occludin and claudin-5 protein secretion on extracellular microvesicles.Scientific reports · 2020Article
- Epigenetics ofCancers · 2020Review
- Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells.Neuroscience bulletin · 2019Article
- NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation.Frontiers in pharmacology · 2019Article
- Characterization of human fetal brain endothelial cells reveals barrier properties suitable for in vitro modeling of the BBB with syngenic co-cultures.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti-inflammatory agent: implications for neuroinflammation.Journal of neuroinflammation · 2018Article
- Article
- Involvement of Ubiquitin-Editing Protein A20 in Modulating Inflammation in Rat Cochlea Associated with Silver Nanoparticle-Induced CD68 Upregulation and TLR4 Activation.Nanoscale research letters · 2016Article
- PARP inhibition in leukocytes diminishes inflammation via effects on integrins/cytoskeleton and protects the blood-brain barrier.Journal of neuroinflammation · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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 conformational form of very late antigen 4 after stimulation with a peptide mimicking monocyte engagement by vascular cell adhesion molecule-1. Peptide stimulation resulted in a 14- to 20-fold up-regulation of the active form of integrin in monocytes that was suppressed by GSK3β inhibitors (40% to 60%). Because small GTPases, such as Rac1, control leukocyte movement, we measured active Rac1 after monocyte activation with relevant stimuli. Stimulation enhanced the level of active Rac1 that was diminished by GSK3β inhibitors. Monocytes treated with GSK3β inhibitors showed increased levels of inhibitory sites of the actin-binding protein, cofilin, and vasodilator-stimulated phosphoprotein-regulating conformational changes of integrins. These results indicate that GSK3β inhibition in monocytes affects active integrin expression, cytoskeleton rearrangement, and adhesion via suppression of Rac1-diminishing inflammatory leukocyte responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.