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The TWNT-4 cells were confirmed to express platelet-derived growth factorβreceptro (PDGF-βR) and α-smooth muscle actin (α-SMA) by immunostaining. Interferonγ (IFNγ), which is known inhibit human hepatic stellate cell activation, could not inhibit collagen type 1 (α1) under a condition of 24 hour incubation at more than 1000 U/ml concentration. Incubation of IFNγ at a low concentration of 100 U/ml, for 14 days, however, inhibit collagen type I (α1) production in both RNA and protein levels. An immunosuprressive agent Rapa, also inhibited collagen type 1 (α1) production proportionally at a concentration of 1 to 10 nt/ml. When both IFNγ and Rapa were added to the incubation medium for 14 days at the one tenth of the usual concentration of each drug, collagen type 1 (α1) expression was equally inhibited. IFNγ and Rapa also inhibited production of TGF-β1 hepatic stellate cell PDGF-βR, and α-SMA. apoptosis of TWNT-4 cells occurred as a result of adenovirus-mediated TRAIL cDNA transfer. These results confirmed that IFNγ and Rapa inhibit collagen expression in hepatic stellate cells, resulting in an antifibrosis effect. 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不死化ヒト肝星細胞モデルを用いたIFNγ及びrapamycinによる肝線維化抑制効果
https://kwmed.repo.nii.ac.jp/records/1266
https://kwmed.repo.nii.ac.jp/records/126691581841-0568-4fea-a052-de011e2b8007
名前 / ファイル | ライセンス | アクション |
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KJ00001725525.pdf (1.9 MB)
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Item type | [ELS]学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-01-23 | |||||
タイトル | ||||||
言語 | ja | |||||
タイトル | 不死化ヒト肝星細胞モデルを用いたIFNγ及びrapamycinによる肝線維化抑制効果 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Antifibrosis Effect of Interferonγ (IFNγ) and Rapamycin (Rapa) in Immortal Human Hepatic Stellate Cells | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
柴田, 憲邦
× 柴田, 憲邦× SHIBATA, Norikuni |
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著者所属(日) | ||||||
ja | ||||||
川崎医科大学内科消化器I部門 | ||||||
著者所属(英) | ||||||
en | ||||||
Division of Gastroenterology, Department of Medicine, Kawasaki Medical School | ||||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | TWNT-4 cell | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Interferonγ | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Rapamycin | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Antifibrosis effect | |||||
記事種別(日) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 原著 | |||||
言語 | ja | |||||
抄録(日) | ||||||
ja | ||||||
interferonγ(IFNγ)とrapamycin (Rapa)による抗肝線維化効果を検討するためヒト肝星細胞を不死化した培養細胞(TWNT-4細胞)を用いて基礎的検討をおこなった.TWNT-4細胞はヒト肝星細胞LI90細胞にhuman telomerase reverse transcriptase (hTERT)を導入することによって作成した.TWNT-4はplatelet derived growth factor βreceptor (PDGF-βR), α-smooth muscle actin (α-SMA), collagen type 1 (α1)を発現しており活性化肝星細胞の形態を呈する.肝星細胞を抑制する事が知られているIFNγを1000U/ml以上の濃度で24時間曝露してもcollagen type 1 (α1)の発現はほとんど低下しなかった.しかしながらIFNγを100U/mlの低濃度でも14日間曝露するとcollagen type1 (α1)の産生はRNA及び蛋白レベルで低下した.免疫抑制剤でもあるRapaも1-10ng/mlの範囲で用量依存的にcollagen type 1 (α1)の産生の抑制がみられた.さらにIFNγ10U/mlとRapa 0.1ng/mlの極めて低い濃度を併用して14日間曝露すると単独群で変わらずcollagen type 1 (α1)の抑制が認められた.すなわちIFNγとRapaの併用では各々の毒性を無視できる低濃度でもcollagen type 1 (α1)の抑制を認める事が明らかとなった.さらにIFNγとRapaは肝星細胞の活性化マーカーであるPDGF-βRとα-SMAを抑制する事,培養細胞上清中へのtransforming growth factor beta 1 (TGF-β1)分泌を抑える事を示した.アデノウイルスベクターを用いてTNF-related apoptosis inducing ligand (TRAIL)をTWNT-4細胞に形質導入することによりアポトーシスに陥らせることができた.これらの実験結果からIFNγとRapaは活性化肝星細胞に作用して肝線維化を抑制し,TRAILはアポトーシスの誘導をもたらす可能性が明らかとなった.今後これらの薬剤を用いて肝硬変における抗肝線維化治療への臨床応用が期待される. | ||||||
抄録(英) | ||||||
en | ||||||
To examine the antifibrosis effect of interferonγ (IFNγ) and Rapa an immortalized human hepatic stellate cell line, TWNT-4, was established by introducing human telomerase reverse transcriptase (hTERT) into LI 90 cells. The TWNT-4 cells were confirmed to express platelet-derived growth factorβreceptro (PDGF-βR) and α-smooth muscle actin (α-SMA) by immunostaining. Interferonγ (IFNγ), which is known inhibit human hepatic stellate cell activation, could not inhibit collagen type 1 (α1) under a condition of 24 hour incubation at more than 1000 U/ml concentration. Incubation of IFNγ at a low concentration of 100 U/ml, for 14 days, however, inhibit collagen type I (α1) production in both RNA and protein levels. An immunosuprressive agent Rapa, also inhibited collagen type 1 (α1) production proportionally at a concentration of 1 to 10 nt/ml. When both IFNγ and Rapa were added to the incubation medium for 14 days at the one tenth of the usual concentration of each drug, collagen type 1 (α1) expression was equally inhibited. IFNγ and Rapa also inhibited production of TGF-β1 hepatic stellate cell PDGF-βR, and α-SMA. apoptosis of TWNT-4 cells occurred as a result of adenovirus-mediated TRAIL cDNA transfer. These results confirmed that IFNγ and Rapa inhibit collagen expression in hepatic stellate cells, resulting in an antifibrosis effect. Therefore these drugs could have a clinical application for the prevention of fibrosis in liver cirrhosis. | ||||||
書誌情報 |
ja : 川崎医学会誌 en : Kawasaki medical journal 巻 28, 号 3, p. 185-197, 発行日 2002 |
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URL | ||||||
識別子 | http://igakkai.kms-igakkai.com/wp/wp-content/uploads/2002/KMJ28(3)185-197.2002.pdf | |||||
識別子タイプ | URI | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.11482/KMJ28(3)185-197.2002.pdf | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0386-5924 | |||||
ISSN | ||||||
収録物識別子タイプ | EISSN | |||||
収録物識別子 | 2758-089X | |||||
雑誌書誌ID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AN00045593 | |||||
雑誌書誌ID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AN12940574 | |||||
著者版フラグ | ||||||
出版タイプ | VoR |