title: TNF-α inhibits the growth of Legionella pneumophila in airway epithelial cells by inducing apoptosis.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kawamoto
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan. Electronic address: y-morina@nagasaki-u.ac.jp.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Kaku
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kosai
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uno
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 851-2128, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D016952:Legionella pneumophila / Q000254:growth & development*; D007877:Legionnaires' Disease / Q000378:metabolism / Q000382:microbiology*; D011014:Pneumonia / Q000378:metabolism / Q000382:microbiology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D053179:Caspase 7
keywords: Anti-TNF-α therapy; Caspase 3; Caspase 7; Cell death; Lung epithelial cells