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ID 53674
JaLCDOI
フルテキストURL
Thumnail 69_5_279.pdf 5.97 MB
著者
Saito, Yukie Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fujii, Yousuke Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yashiro, Masato Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsuge, Mitsuru Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nosaka, Nobuyuki Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamashita, Nobuko Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamada, Mutsuko Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsukahara, Hirokazu Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Morishima, Tsuneo Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
抄録
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.
キーワード
pulmonary microvascular endothelial cells
permeability
edaravone
vascular endothelial-cadherin
zonula occludens-1 protein
Amo Type
Original Article
発行日
2015-10
出版物タイトル
Acta Medica Okayama
69巻
5号
出版者
Okayama University Medical School
開始ページ
279
終了ページ
290
ISSN
0386-300X
NCID
AA00508441
資料タイプ
学術雑誌論文
言語
English
著作権者
CopyrightⒸ 2015 by Okayama University Medical School
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Sience KeyUT