ID 53674
JaLCDOI
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Thumnail 69_5_279.pdf 5.97 MB
Author
Saito, Yukie
Tsuge, Mitsuru
Nosaka, Nobuyuki
Yamashita, Nobuko Kaken ID researchmap
Yamada, Mutsuko
Tsukahara, Hirokazu Kaken ID researchmap
Morishima, Tsuneo
Abstract
Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α+IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.
Keywords
pulmonary microvascular endothelial cells
permeability
edaravone
vascular endothelial-cadherin
zonula occludens-1 protein
Amo Type
Original Article
Published Date
2015-10
Publication Title
Acta Medica Okayama
Volume
volume69
Issue
issue5
Publisher
Okayama University Medical School
Start Page
279
End Page
290
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2015 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Science KeyUT