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Identification of Helicobacter pylori VacA in human lung and its effects on lung cells

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Title: Identification of Helicobacter pylori VacA in human lung and its effects on lung cells
Authors: Nakashima, Shota / Kakugawa, Tomoyuki / Yura, Hirokazu / Tomonaga, Masaomi / Harada, Tatsuhiko / Hara, Atsuko / Hara, Shintaro / Nakano, Masayuki / Yamasaki, Eiki / Sakamoto, Noriho / Ishimatsu, Yuji / Isomoto, Hajime / Gochuico, Bernadette R. / Suffredini, Anthony F. / Mukae, Hiroshi / Kurazono, Hisao / Hirayama, Toshiya / Moss, Joel / Kohno, Shigeru
Issue Date: 8-May-2015
Publisher: Academic Press Inc.
Citation: Biochemical and Biophysical Research Communications, 460(3), pp.721-726; 2015
Abstract: Objective: Prior reports suggested that infection with Helicobacter pylori was associated with respiratory diseases; pathogenetic mechanisms however, were not defined. We tested the hypothesis that VacA, an exotoxin of H. pylori, a gastric pathogen, was aspirated into the lung and could stimulate secretion of inflammatory cytokines by lung epithelial cells. Methods: The presence of VacA was determined by immunohistochemistry in surgical lung biopsy tissue samples from 72 patients with interstitial pneumonia. The effects of VacA on A549 human alveolar epithelial adenocarcinoma cells and normal human bronchial epithelial cells were determined. After incubation with VacA, the secretions of cytokines were measured by Multiplex Luminex® Assays. Results: VacA was detected with anti-VacA antibodies in bronchial epithelial cells and alveolar epithelial cells from 10 of 72 patients with interstitial pneumonia. VacA was more prevalent in lungs of patients with collagen vascular disease-associated interstitial pneumonia than in those of patients with idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia and cryptogenic organizing pneumonia. Incubation of A549 cells and normal human bronchial epithelial cells with VacA for 24 h was cytotoxic, and resulted in vacuolation. VacA induced interleukin-8 production by A549 cells and normal human bronchial epithelial cells and interleukin-6 production by A549 cells. Based on multiplex screening, interleukin-8 and interleukin-6 were the primary secretory products induced by VacA. Conclusions: H. pylori VacA is present in human lung and can induce interleukin-8 and interleukin-6 production by human lung cells. VacA could have a role in the pathogenesis of respiratory diseases by its cytotoxic effects and by inducing the secretion of interleukin-8 and interleukin-6 by targeted airway epithelial cells.
Keywords: A549 cells / Helicobacter pylori / Interleukin-6 / Interleukin-8 / Normal human bronchial epithelial cells / VacA
URI: http://hdl.handle.net/10069/35785
ISSN: 0006291X
DOI: 10.1016/j.bbrc.2015.03.096
Rights: © 2015 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35785

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