Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall

AbstractImpairments of the blood brain barrier (BBB) and vascular dysfunction contribute to Alzheimer’s disease (AD) from the earliest stages. However, the effects of AD-affected astrocytes on the BBB remain largely unexplored. In the present study we created an in vitro BBB using human immortalised endothelial cells in combination with immortalised astroglial cell lines from the hippocampus of 3xTG-AD and wild-type mice (3Tg-iAstro and WT-iAstro, respectively). We found that co-culturing endothelial monolayers with WT-iAstro up-regulates expression of endothelial tight junction proteins (claudin-5, occludin, ZO-1) and increases the trans-endothelial electrical resistance (TEER). In contrast, co-culturing with 3Tg-iAstro does not affect expression of tight junction proteins and does not change the TEER of endothelial monolayers. The same in vitro model has been used to evaluate the effects of extracellular vesicles (EVs) derived from the WT-iAstro and 3Tg-iAstro. The EVs derived from WT-iAstro increased TEER and up-regulated expression of tight junction proteins, whereas EVs from 3Tg-iAstro were ineffective. In conclusion, we show for the first time that immortalised hippocampal astrocytes from 3xTG-AD mice exhibit impaired capacity to support BBB integrity in vitro through paracrine mechanisms and may represent an important factor underlying vascular abnormalities during development of AD.

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Evidence that gene expression of ovarian follicular tight junction proteins is regulated in vivo and in vitro in cattle

Journal of Animal Science ◽

10.2527/jas2016.0892 ◽

2017 ◽

Vol 95 (3) ◽

pp. 1313 ◽

Cited By ~ 7

Author(s):

L. Zhang ◽

L. F. Schütz ◽

C. L. Robinson ◽

M. L. Totty ◽

L. J. Spicer

Keyword(s):

Gene Expression ◽

Tight Junction ◽

Tight Junction Proteins ◽

Junction Proteins

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Murine bone marrow-derived dendritic cells as a potential in vitro model for predictive identification of chemical sensitizers

Toxicology Letters ◽

10.1016/j.toxlet.2007.09.012 ◽

2007 ◽

Vol 175 (1-3) ◽

pp. 89-101 ◽

Cited By ~ 13

Author(s):

E PEPIN ◽

M GOUTET ◽

M BAN

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

In Vitro Model ◽

Murine Bone Marrow ◽

Vitro Model

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Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation

Journal of Investigative Dermatology ◽

10.1038/jid.2015.58 ◽

2015 ◽

Vol 135 (7) ◽

pp. 1790-1800 ◽

Cited By ~ 34

Author(s):

Caroline Stremnitzer ◽

Krisztina Manzano-Szalai ◽

Anna Willensdorfer ◽

Philipp Starkl ◽

Mario Pieper ◽

...

Keyword(s):

Tight Junction ◽

Enzymatic Activity ◽

Human Keratinocytes ◽

Tight Junction Proteins ◽

Tlr4 Activation ◽

Junction Proteins

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MicroRNA-30a regulates acute cerebral ischemia-induced blood–brain barrier damage through ZnT4/zinc pathway

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20926787 ◽

2020 ◽

pp. 0271678X2092678 ◽

Cited By ~ 1

Author(s):

Peng Wang ◽

Rong Pan ◽

John Weaver ◽

Mengjie Jia ◽

Xue Yang ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Tight Junction ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Tight Junction Proteins ◽

Blood Brain ◽

Acute Cerebral Ischemia ◽

Junction Proteins

The mechanism of early blood–brain barrier (BBB) disruption after stroke has been intensively studied but still not fully understood. Here, we report that microRNA-30a (miR-30a) could mediate BBB damage using both cellular and animal models of ischemic stroke. In the experiments in vitro, inhibition of miR-30a decreased BBB permeability, prevented the degradation of tight junction proteins, and reduced intracellular free zinc in endothelial cells. We found that the zinc transporter ZnT4 was a direct target of negative regulation by miR-30a, and ZnT4/zinc signaling pathway contributed significantly to miR-30a-mediated BBB damage. Consistent with these in vitro findings, treatment with miR-30a inhibitor reduced zinc accumulation, increased the expression of ZnT4, and prevented the loss of tight junction proteins in microvessels of ischemic animals. Furthermore, inhibition of miR-30a, even at 90 min post onset of middle cerebral artery occlusion, prevented BBB damage, reduced infarct volume, and ameliorated neurological deficits. Together, our findings provide novel insights into the mechanisms of cerebral ischemia-induced BBB disruption and indicate miR-30a as a regulator of BBB function that can be an effective therapeutic target for ischemic stroke.

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