神戸大学附属図書館デジタルアーカイブ
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https://doi.org/10.24546/81000138
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2024-04-27
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81000138 (fulltext)
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メタデータID
81000138
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open access
出版タイプ
Version of Record
タイトル
Low-dose Warfarin Functions as an Immunomodulator to Prevent Cyclophosphamide-induced NOD Diabetes
著者
Kurohara, Midori ; Yasuda, Hisafumi ; Moriyama, Hiroaki ; Nakayama, Maki ; Sakata, Muneaki ; Yamada, Katsumi ; Kotani, Reiko ; Hara, Kenta ; Yokono, Koichi ; Nagata, Masao
著者名
Kurohara, Midori
著者名
Yasuda, Hisafumi
著者名
Moriyama, Hiroaki
著者名
Nakayama, Maki
著者名
Sakata, Muneaki
著者名
Yamada, Katsumi
著者名
Kotani, Reiko
著者名
Hara, Kenta
著者名
Yokono, Koichi
著者名
Nagata, Masao
収録物名
The Kobe journal of the medical sciences
巻(号)
54(1)
ページ
1-13
出版者
神戸大学医学部
Kobe University School of Medicine
刊行日
2008
公開日
2008-02-20
抄録
Warfarin has been used as an anticoagulant for a long time. Recently, thepleiotropic effect of warfarin has been investigated. As low-dose warfarin has beenreported to have anti-inflammatory effect through suppression of IL-6 secretion andinhibit the immune-associated signal between Tyro3 and its ligand, Gas6, the effect oflow-dose warfarin on autoimmune diabetes in NOD mice was examined. To investigatethe anti-inflammatory effect of warfarin, IL-6 secretion by splenocytes was examined inthe presence of various concentrations of warfarin. Low concentration of warfarininhibited IL-6 secretion. mRNA expression of Rse, one of the Tyro3 receptor familymembers, and Gas6 were analyzed in NOD mice. It was detected in islets, splenocytesand bone-marrow derived dendritic cells. 0.25 mg/l or 0.50 mg/l of warfarin was orallyadministered to NOD mice as a cyclophosphamide-induced diabetes model. Oraladministration of warfarin at much lower doses than those clinically used as ananticoagulant significantly reduced the degree of insulitis and diabetes incidence in thismodel. We previously demonstrated that anti-FasL Ab-treatment led to completeprevention of autoimmune diabetes in NOD mice. As Fas/FasL signaling is reported tobe essential for cyclophosphamide-induced diabetes model, we extracted RNA fromlymphocytes of the inguinal lymph nodes of anti-FasL Ab-treated NOD mice andperformed real-time PCR to determine expression of Rse gene. Interestingly, theexpression of Rse gene related to the blockade of Fas/FasL signaling was reduced to lessthan half the level of untreated mice. In conclusion, low-dose warfarin is a potentialimmunomodulator which can prevent autoimmune diabetes.
キーワード
Type 1 diabetes
NOD mouse
cyclophosphamide
IL-6
Gas6
カテゴリ
The Kobe journal of the medical sciences
>
54巻
>
54巻1号(2008)
紀要論文
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資源タイプ
departmental bulletin paper
言語
English (英語)
ISSN
0023-2513
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CiNiiで学外所蔵を検索
NCID
AA00711740
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関連情報
NAID
110006648210
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URI
http://www.med.kobe-u.ac.jp/journal/contents.html
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