並列タイトル等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
タイトル(掲載誌)Journal of Infection and Chemotherapy
授与機関名Nagasaki University (長崎大学)
一般注記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.
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
Nagasaki University (長崎大学), 博士(医学) (2017-02-22)
DOIinfo:doi/10.1016/j.jiac.2016.09.010
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