Interactions between macrophages and brain microvascular endothelial cells: role in pathogenesis of HIV-1 infection and blood-brain barrier function

1999 ◽  
Vol 5 (6) ◽  
pp. 659-669 ◽  
Author(s):  
Hans SLM Nottet
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Microvascular Endothelial ◽  
Hiv 1

scholarly journals Astrocyte-Derived TGFβ1 Facilitates Blood–Brain Barrier Function via Non-Canonical Hedgehog Signaling in Brain Microvascular Endothelial Cells

2021 ◽  
Vol 11 (1) ◽  
pp. 77
Author(s):  
Jiyang Fu ◽  
Liang Li ◽  
Dong Huo ◽  
Shuli Zhi ◽  
Ruicheng Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Intercellular Communication ◽  
Barrier Function ◽  
Hedgehog Signaling ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Microvascular Endothelial

The blood–brain barrier is a specialized structure in mammals, separating the brain from the bloodstream and maintaining the homeostasis of the central nervous system. The barrier is composed of various types of cells, and the communication between these cells is critical to blood–brain barrier (BBB) function. Here, we demonstrate the astrocyte-derived TGFβ1-mediated intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). By using an in vitro co-culture model, we observed that the astrocyte-derived TGFβ1 enhanced the tight junction protein ZO-1 expression in BMECs and the endothelial barrier function via a non-canonical hedgehog signaling. Gli2, the core transcriptional factor of the hedgehog pathway, was demonstrated to modulate ZO-1 expression directly. By the dual-luciferase reporter system and chromatin immunoprecipitation, we further identified the exact sites on Smad2/3 that bound to the gli2 promotor and on Gli2 that bound to the zo-1 promotor. Our work highlighted the TGFβ1-mediated intercellular communication of astrocytes with BMECs in BBB, which shall extend current knowledge on the BBB homeostasis physiologically, and more importantly suggests TGFβ1 as a potential effector for future prevention and amelioration of BBB dysfunction.

scholarly journals Differential Effects of Tat Proteins Derived from HIV-1 Subtypes B and Recombinant CRF02_AG on Human Brain Microvascular Endothelial Cells: Implications for Blood–Brain Barrier Dysfunction

2014 ◽  
Vol 34 (6) ◽  
pp. 1047-1059 ◽  
Author(s):  
Shawna M Woollard ◽  
Biju Bhargavan ◽  
Fang Yu ◽  
Georgette D Kanmogne
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Genetic Differences ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Microvascular Endothelial ◽  
Hiv 1

HIV-1 genetic differences influence viral replication and progression to AIDS. HIV-1 circulating recombinant form (CRF)02_AG is the predominant viral subtype infecting humans in West and Central Africa, but its effects on HIV neuropathogenesis are not known. In the present study, we investigated the effects of Tat proteins from HIV-1 subtype B (Tat.B) and HIV-1 CRF02_AG (Tat.AG) on primary human brain microvascular endothelial cells (HBMEC), the major component of the blood–brain barrier (BBB). Using Affymetrix GeneChip Human Gene 1.0.ST arrays, we showed that Tat.AG had minimal effects while Tat.B induced transcriptional upregulation of 90 genes in HBMEC, including proinflammatory chemokines, complement components C3, C7, and complement factor B, matrix metalloproteinases (MMP)-3, MMP-10, and MMP-12. These results were confirmed by real-time PCR. Compared with Tat.AG, Tat.B significantly increased MMP-3, MMP-10, and MMP-12 activities in HBMEC, and the MMPs tissue inhibitor of metalloproteinase-2 blocked Tat-induced increase in MMPs activity. Western blot analyses also showed that Tat increased the expression of C3 and its cleaved fragment C3b in HBMEC. These data suggest that genetic differences between HIV-1 subtypes B and CRF02_AG influence the effects of Tat proteins from these two clades on HBMEC, including molecular and cellular functions, and canonical pathways, which would affect BBB dysfunction and viral neuropathogenesis.

Anthropogenic Iron Oxide Nanoparticles Induce Damage to Brain Microvascular Endothelial Cells Forming the Blood-Brain Barrier

2021 ◽  
Author(s):  
Lorena Gárate-Vélez ◽  
Claudia Escudero-Lourdes ◽  
Daniela Salado-Leza ◽  
Armando González-Sánchez ◽  
Ildemar Alvarado-Morales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Fe3o4 Nps ◽  
Microvascular Endothelial ◽  
The Brain

Background: Iron nanoparticles, mainly in magnetite phase (Fe3O4 NPs), are released to the environment in areas with high traffic density and braking frequency. Fe3O4 NPs were found in postmortem human brains and are assumed to get directly into the brain through the olfactory nerve. However, these pollution-derived NPs may also translocate from the lungs to the bloodstream and then, through the blood-brain barrier (BBB), into the brain inducing oxidative and inflammatory responses that contribute to neurodegeneration. Objective: To describe the interaction and toxicity of pollution-derived Fe3O4 NPs on primary rat brain microvascular endothelial cells (rBMECs), main constituents of in vitro BBB models. Methods: Synthetic bare Fe3O4 NPs that mimic the environmental ones (miFe3O4) were synthesized by co-precipitation and characterized using complementary techniques. The rBMECs were cultured in Transwell® plates. The NPs-cell interaction was evaluated through transmission electron microscopy and standard colorimetric in vitro assays. Results: The miFe3O4 NPs, with a mean diameter of 8.45 ± 0.14 nm, presented both magnetite and maghemite phases, and showed super-paramagnetic properties. Results suggest that miFe3O4 NPs are internalized by rBMECs through endocytosis and that they are able to cross the cells monolayer. The lowest miFe3O4 NPs concentration tested induced mid cytotoxicity in terms of 1) membrane integrity (LDH release) and 2) metabolic activity (MTS transformation). Conclusion: Pollution-derived Fe3O4 NPs may interact and cross the microvascular endothelial cells forming the BBB and cause biological damage.

scholarly journals ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells

2017 ◽  
Vol 38 (5) ◽  
pp. 809-822 ◽  
Author(s):  
Hu Zhang ◽  
Shuhong Zhang ◽  
Jilin Zhang ◽  
Dongxin Liu ◽  
Jiayi Wei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Down Regulation ◽  
Gm Csf ◽  
Blood Brain ◽  
Microvascular Endothelial

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer’s disease, and multiple sclerosis. We previously reported that in Alzheimer’s disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood–brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood–brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

scholarly journals GRP78 antibodies damage the blood–brain barrier and relate to cerebellar degeneration in Lambert-Eaton myasthenic syndrome

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2253-2264 ◽  
Author(s):  
Fumitaka Shimizu ◽  
Yukio Takeshita ◽  
Yasuteru Sano ◽  
Yuka Hamamoto ◽  
Hirokazu Shiraishi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Nuclear Factor Κb ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Nuclear Factor ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Myasthenic Syndrome ◽  
Microvascular Endothelial

Abstract Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction caused by autoantibodies binding to P/Q-type voltage-gated calcium channels. Breakdown of the blood–brain barrier and diffusion of cerebellar granule/Purkinje cell-reactive autoantibodies into the CNS are critical for the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome. We recently found evidence that glucose-regulated protein 78 (GRP78) autoantibodies in the plasma of patients with neuromyelitis optica promote the CNS access of AQP4 autoantibodies. In the present study, we investigated whether the GRP78 autoantibodies in PCD-LEMS IgG boost the brain uptake of cerebellar cell-reactive antibodies across the blood–brain barrier and facilitate cerebellar dysfunction. We first evaluated the effects of purified IgG from PCD-LEMS or PCD patients on the blood–brain barrier function in human brain microvascular endothelial cells using a high content imaging system with nuclear factor κB p65 and intracellular adhesion molecule 1 (ICAM1) immunostaining. Next, we identified GRP78 autoantibodies causing blood–brain barrier permeability in PCD-LEMS IgG by co-immunoprecipitation and the living cell-based antibody binding assays. Exposure of brain microvascular endothelial cells to IgG from PCD-LEMS patients induced nuclear factor κB p65 nuclear translocation, ICAM1 upregulation, reduced claudin-5 expression, increased permeability and increased autocrine IL-1β and IL-8 secretion; the IgG from patients with Lambert-Eaton myasthenic syndrome did not have these effects. We detected GRP78 autoantibodies in the IgG of LEMS-PCD (83.3%, n = 18), but observed fewer in patients with LEMS (6.6%, n = 15) and none were observed in the control subjects (n = 8). The depletion of GRP78 autoantibodies reduced the biological effect of LEMS-PCD IgG on brain microvascular endothelial cells. These findings suggest that GRP78 autoantibodies play a role beyond neuromyelitis optica and that they have direct implications in the phenotypic differences between PCD-LEMS and LEMS.

Anthropogenic Iron Oxide Nanoparticles Induce Damage to Brain Microvascular Endothelial Cells Forming the Blood-Brain Barrier

2020 ◽  
Vol 76 (4) ◽  
pp. 1527-1539
Author(s):  
Lorena Gárate-Vélez ◽  
Claudia Escudero-Lourdes ◽  
Daniela Salado-Leza ◽  
Armando González-Sánchez ◽  
Ildemar Alvarado-Morales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Iron Oxide ◽  
Blood Brain Barrier ◽  
Iron Oxide Nanoparticles ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Oxide Nanoparticles ◽  
Brain Microvascular Endothelial Cells ◽  
Blood Brain ◽  
Microvascular Endothelial
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