title: Identification of Helicobacter pylori VacA in human lung and its effects on lung cells.
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.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan. Electronic address: kakugawa@nagasaki-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yura
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tomonaga
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Harada
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hara
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamasaki
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishimatsu
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Isomoto
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.affiliation: Department of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Kurazono
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C074689:VacA protein, Helicobacter pylori
keywords: A549 cells; Helicobacter pylori; Interleukin-6; Interleukin-8; Normal human bronchial epithelial cells; VacA
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