CXCR4 down-regulation by small interfering RNA inhibits invasion and tubule formation of human retinal microvascular endothelial cells

2007 ◽  
Vol 358 (4) ◽  
pp. 990-996 ◽  
Author(s):  
Keming Yu ◽  
Jing Zhuang ◽  
Joseph M. Kaminski ◽  
Bala Ambati ◽  
Qianying Gao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Small Interfering Rna ◽  
Microvascular Endothelial Cells ◽  
Down Regulation ◽  
Tubule Formation ◽  
Microvascular Endothelial ◽  
Interfering Rna

LFA1 Mediated Attachment of Primary Human Monocytes to Activated Brain Microvascular Endothelial Cells Is Regulated by SDF-1α through the SRC Family Kinase Lyn; Potential Involvement of This Signaling Pathway in HIV-Associated Dementia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 516-516
Author(s):  
Mobeen Malik ◽  
Ying-Yu Chen ◽  
Martha F. Kienzle ◽  
Ronald G. Collman ◽  
Andrzej Ptasznik
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Human Monocytes ◽  
Src Family Kinase ◽  
Down Regulation ◽  
Microvascular Endothelial ◽  
Monocyte Adherence

Abstract Infiltration of activated monocytes into the brain of HIV-infected patients is a prerequisite for the development of HIV-associated dementia (HAD). The chemokine stromal derived factor-1α (SDF-1α) is expressed at increased levels in the central nervous system (CNS) of HAD patients and elicits chemotaxis and other cellular effects through its receptor CXCR4. In this project, we investigated the intracellular signaling pathway by which SDF-1α mediates the movement and attachment of monocytes to brain microvascular endothelia, and which may contribute to their infiltration into the CNS in HAD. We demonstrated that SDF-1α stimulates migration of primary human monocytes through its receptor CXCR4, and decreases monocyte adherence to surfaces coated with ICAM-1. SDF-1α also decreases monocyte adherence to brain microvascular endothelial cells (BMVEC) activated with the pro-inflammatory cytokines TNF-α or IL-1β, or with recombinant HIV-1 envelope glycoprotein (gp120), which increase endothelial cells expression of ICAM-1. The decreased monocyte adherence was linked to down regulation of the activation-dependent epitope of the β2 integrin LFA-1 which is a ligand for ICAM-1. We then demonstrated that the Src family kinase Lyn is a central modulator of migration and LFA-1-mediated adhesion of SDF-1α-stimulated primary monocytes. Using siRNA knockdown we achieved 80% down regulation of Lyn kinase in human monocytes. Lyn down regulation decreased SDF-1α-mediated migration and prevented its inhibition of monocyte attachment to ICAM-1 coated surfaces and activated BMVEC. These data indicate that in SDF-1α-stimulated primary human monocytes Lyn is a positive regulator of cell migration, and a negative regulator of cell adhesion to BMVEC by inhibiting the ICAM-1 binding activity of the LFA-1 integrin. Thus, CXCR4-triggered inside-out integrin signaling, through Lyn, inhibits adherence and stimulates movement of monocytes towards SDF-1α gradient on BMVEC monolayers. These results provide new insight into the intracellular signaling cascade that controls primary human monocytes movement and attachment at the blood brain barrier.

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 Small Interfering RNA-mediated Down-regulation of Caveolin-1 Differentially Modulates Signaling Pathways in Endothelial Cells

2004 ◽  
Vol 279 (39) ◽  
pp. 40659-40669 ◽  
Author(s):  
Eva Gonzalez ◽  
Aaron Nagiel ◽  
Alison J. Lin ◽  
David E. Golan ◽  
Thomas Michel
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathways ◽  
Small Interfering Rna ◽  
Down Regulation ◽  
Caveolin 1 ◽  
Interfering Rna

scholarly journals Royal jelly regulates the proliferation of human dermal microvascular endothelial cells through the down-regulation of a photoaging-related microRNA

2019 ◽  
Vol 13 (5) ◽  
pp. 268-273
Author(s):  
Yuya Kawano ◽  
Katsunari Makino ◽  
Masatoshi Jinnin ◽  
Soichiro Sawamura ◽  
Shuichi Shimada ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Royal Jelly ◽  
Microvascular Endothelial Cells ◽  
Down Regulation ◽  
Microvascular Endothelial

Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

2012 ◽  
Vol 82 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Zahide Cavdar ◽  
Mehtap Y. Egrilmez ◽  
Zekiye S. Altun ◽  
Nur Arslan ◽  
Nilgun Yener ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Matrix Metalloproteinase 2 ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Microvascular Endothelial

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

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