JaLCDOI 10.18926/AMO/53674
フルテキストURL 69_5_279.pdf
著者 Saito, Yukie| Fujii, Yousuke| Yashiro, Masato| Tsuge, Mitsuru| Nosaka, Nobuyuki| Yamashita, Nobuko| Yamada, Mutsuko| Tsukahara, Hirokazu| Morishima, Tsuneo|
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 26490025
Web of Sience KeyUT 000365519600004