caa a22 4500 445313307 CHVBK 20180317142637.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s11095-010-0331-3 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0331-3 Positive Correlation Between the Generation of Reactive Oxygen Species and Activation/Reactivation of Transgene Expression After Hydrodynamic Injections into Mice [Elektronische Daten] [Naomi Takiguchi, Yuki Takahashi, Makiya Nishikawa, Yuriko Matsui, Yasushi Fukuhara, Daihi Oushiki, Kazuki Kiyose, Kenjiro Hanaoka, Tetsuo Nagano, Yoshinobu Takakura] ABSTRACT: 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. Springer Science+Business Media, LLC, 2010 hydrodynamic injection nationallicence inflammation nationallicence liver nationallicence plasmid DNA nationallicence reactive oxygen species nationallicence Takiguchi Naomi Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Takahashi Yuki Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Nishikawa Makiya Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Matsui Yuriko Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Fukuhara Yasushi Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Oushiki Daihi Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut Kiyose Kazuki Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut Hanaoka Kenjiro Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut Nagano Tetsuo Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut Takakura Yoshinobu Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 702-711 0724-8741 28:4<702 2011 28 11095 https://doi.org/10.1007/s11095-010-0331-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0331-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takiguchi Naomi Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 700 1- Takahashi Yuki Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 700 1- Nishikawa Makiya Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 700 1- Matsui Yuriko Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 700 1- Fukuhara Yasushi Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 700 1- Oushiki Daihi Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut NATIONALLICENCE 700 1- Kiyose Kazuki Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut NATIONALLICENCE 700 1- Hanaoka Kenjiro Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut NATIONALLICENCE 700 1- Nagano Tetsuo Department of Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences and Chemical Biology Research Initiative, The University of Tokyo, Tokyo, Japan aut NATIONALLICENCE 700 1- Takakura Yoshinobu Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/4(2011-04-01), 702-711 0724-8741 28:4<702 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer