Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection
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- Hideyuki Yanai
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Atsushi Matsuda
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Jianbo An
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Ryuji Koshiba
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Junko Nishio
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Hideo Negishi
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Hiroaki Ikushima
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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- Takashi Onoe
- Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan; and
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- Hideki Ohdan
- Department of Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan; and
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- Nobuaki Yoshida
- Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
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- Tadatsugu Taniguchi
- Department of Molecular Immunology, Institute of Industrial Science, University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan;
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説明
<jats:title>Significance</jats:title> <jats:p> The high-mobility group box 1 (HMGB1) protein is abundantly expressed in the nucleus where it regulates chromatin function. More recently, it was found to also function in the cytoplasm and extracellular milieu for the regulation of immunity and inflammation. However, the in vivo study of HMGB1 has been hampered by the fact that HMGB1-deficient mice die soon after birth. In this study, we successfully generated <jats:italic>Hmgb1</jats:italic> -floxed mice to achieve conditional inactivation of the gene in a cell- and tissue-specific manner. We demonstrate that cytosolic HMGB1 in myeloid cells is critical for the protection of the host from endotoxemia and bacterial infection by inducing autophagy, a cellular response critical for maintaining cellular viability in the setting of various stresses including infection. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (51), 20699-20704, 2013-12-03
Proceedings of the National Academy of Sciences