Abstracts

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

by




Institution: Nagasaki University /
Department:
Year: 2016
Keywords: Anti-TNF- therapy; Cell death; Caspase 3; Caspase 7; Lung epithelial cells
Posted: 02/01/2018
Record ID: 2160690
Full text PDF: http://hdl.handle.net/10069/37166


Abstract

Background: TNF- plays an important role in the pathogenesis of Legionella pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF- 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- 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-. 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- treatment of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF- on Lp replication were suppressed after treatment with a TNF--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- 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- 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- therapy who develop pneumonia.