ニシオ　ジュンコ   Nishio Junko   西尾　純子    所属   東邦大学  医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America
掲載区分	国外
巻・号・頁	110(51),pp.20699-704
著者・共著者	Hideyuki Yanai,Atsushi Matsuda,Jianbo An,Ryuji Koshiba,Junko Nishio,Hideo Negishi,Hiroaki Ikushima,Takashi Onoe,Hideki Ohdan,Nobuaki Yoshida,Tadatsugu Taniguchi
発行年月	2013/12/17
概要	High-mobility group box 1 (HMGB1) is a DNA-binding protein abundantly expressed in the nucleus that has gained much attention for its regulation of immunity and inflammation. Despite this, whether and how HMGB1 contributes to protective and/or pathological responses in vivo is unclear. In this study, we constructed Hmgb1-floxed (Hmgb1(f)(/f)) mice to achieve the conditional inactivation of the gene in a cell- and tissue-specific manner by crossing these mice with an appropriate Cre recombinase transgenic strain. Interestingly, although mice with HMGB1 ablation in myeloid cells apparently develop normally, they are more sensitive to endotoxin shock compared with control mice, which is accompanied by massive macrophage cell death. Furthermore, these mice also show an increased sensitivity to Listeria monocytogenes infection. We also provide evidence that the loss of HMGB1 in macrophages results in the suppression of autophagy, which is commonly induced by lipopolysaccharide stimulation or L. monocytogenes infection. Thus, intracellular HMGB1 contributes to the protection of mice from endotoxemia and bacterial infection by mediating autophagy in macrophages. These newly generated HMGB1 conditional knockout mice will serve a useful tool with which to study further the in vivo role of this protein in various pathological conditions.
DOI	10.1073/pnas.1320808110
PMID	24302768