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タイトル: Positive correlation between the generation of reactive oxygen species and activation/reactivation of transgene expression after hydrodynamic injections into mice.
著者: Takiguchi, Naomi
Takahashi, Yuki  kyouindb  KAKEN_id
Nishikawa, Makiya  kyouindb  KAKEN_id
Matsui, Yuriko
Fukuhara, Yasushi
Oushiki, Daihi
Kiyose, Kazuki
Hanaoka, Kenjiro
Nagano, Tetsuo
Takakura, Yoshinobu  kyouindb  KAKEN_id
著者名の別形: 高橋, 有己
高倉, 喜信
キーワード: hydrodynamic injection
inflammation
liver
plasmid DNA
reactive oxygen species
発行日: Apr-2011
出版者: Springer Science+Business Media, LLC
誌名: Pharmaceutical research
巻: 28
号: 4
開始ページ: 702
終了ページ: 711
抄録: Purpose : Hydrodynamic injection has been shown to reactivate silenced transgene expression in mouse liver. In this study, the roles of inflammatory cytokines and reactive oxygen species (ROS) in the reactivation were examined. Methods : Production of inflammatory cytokines and ROS by hydrodynamic injection of saline was examined in mice that had received a hydrodynamic injection of a plasmid expressing Gaussia luciferase. The level of reporter gene expression was used as an indicator of the reactivation. The involvement of cytokines and ROS was examined by depleting Kupffer cells or by pre-administration of antioxidants, respectively. Results : A hydrodynamic injection of saline induced a significant production of interleukin (IL)-6. Depleting Kupffer cells using clodronate liposomes markedly reduced the IL-6 production but had no significant effect on the transgene expression. On the other hand, an injection of catalase or N-acetylcysteine significantly inhibited the hydrodynamic injection-induced reactivation of silenced transgene expression. The silenced expression was also reactivated by carbon tetrachloride, an inducer of oxidative stress in the liver, in a dose-dependent manner, and this reactivation was significantly inhibited by catalase. Conclusions : These findings show a positive correlation between the generation of ROS and the reactivation of silenced transgene expression after hydrodynamic injections.
著作権等: The final publication is available at www.springerlink.com
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/159458
DOI(出版社版): 10.1007/s11095-010-0331-3
PubMed ID: 21116691
出現コレクション:学術雑誌掲載論文等

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