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TNF-α inhibits the growth of Legionella pneumophila in airway epithelial cells by inducing apoptosis


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タイトル: TNF-α inhibits the growth of Legionella pneumophila in airway epithelial cells by inducing apoptosis
その他のタイトル: TNF-αは、アポトーシスを誘導することでLegionella pneumophilaの気道上皮細胞内での増殖を抑制する
著者: 川元, 康嗣
著者(別表記) : Kawamoto, Yasuhide
発行日: 2017年 2月22日
出版者: Elsevier
引用: Nagasaki University (長崎大学), 博士(医学) (2017-02-22)
抄録: Background: TNF-α plays an important role in the pathogenesis of Legionella pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF-α therapy are at an increased risk of Lp infection. Lp infects both phagocytic and non-phagocytic cells such as airway epithelial cells; however, the role of TNF-α in airway epithelial cells is unknown. Methods: Human airway epithelial cell line NCI-H292 was infected with Lp NUL1 strain. After infection, both intracellular growth of Lp and cell death were evaluated after treating the cells with or without TNF-α. Apoptosis was examined by performing activated caspase-3/7 staining and by using a pan-caspase inhibitor. Results: Lp infected and replicated in NCI-H292 cells in a time-dependent manner, and TNF-α treatment of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF-α on Lp replication were suppressed after treatment with a TNF-α-neutralizing antibody. Lp infection increased extracellular lactate dehydrogenase levels and decreased the number of living cells. Increased number of Lp-infected NCI-H292 cells showed caspase-3/7 activation, indicating they underwent apoptosis. TNF-α treatment inhibited Lp replication by increasing the apoptosis of NCI-H292 cells. Conclusions: Thus, our results suggested that airway epithelial cells were involved in the pathogenesis of Lp infection and that TNF-α played a protective role by inhibiting the intracellular replication of Lp and by increasing the apoptosis of Lp-infected airway epithelial cells. However, Lp infection should be investigated further in patients undergoing anti-TNF-α therapy who develop pneumonia.
記述: 長崎大学学位論文 学位記番号:博(医歯薬)甲第927号 学位授与年月日:平成29年2月22日 / Author: Yasuhide Kawamoto, Yoshitomo Morinaga, Yumiko Kimura, Norihito Kaku, Kosuke Kosai, Naoki Uno, Hiroo Hasegawa, Katsunori Yanagihara / Citation: Journal of Infection and Chemotherapy, 23(1), pp.51–55; 2017
キーワード: Anti-TNF-α therapy / Cell death / Caspase 3 / Caspase 7 / Lung epithelial cells
URI: http://hdl.handle.net/10069/37166
ISSN: 1341321X
DOI: 10.1016/j.jiac.2016.09.010
権利: © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
資料タイプ: Thesis or Dissertation
原稿種類: ETD
出現コレクション:110 学位論文

引用URI : http://hdl.handle.net/10069/37166

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