title: Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. pylori exposed gastric epithelial cells.
abstract: BACKGROUND
  The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA⁻ H. pylori variants.
  
  
  RESULTS
  Interleukin-8 was the most significantly up-regulated gene and appears to play a paramount role in the epithelial cell response to H. pylori infection and in the pathological processes leading to gastric disease. MAPK and NF-kappaB cellular pathways were powerfully activated, but did not seem to explain the impressive IL-8 response. There was marked up-regulation of TP53BP2, whose corresponding protein ASPP2 may interact with H. pylori CagA and cause marked p53 suppression of apoptosis. Other regulators of apoptosis also showed abberant regulation. We also identified up-regulation of several oncogenes and down-regulation of tumor suppressor genes as early as during the first 24 h of infection. H. pylori OMPLA phase variation did not seem to influence the inflammatory epithelial cell gene response in this experiment.
  
  
  CONCLUSIONS
  In whole genome analysis of the epithelial response to H. pylori exposure, IL-8 demonstrated the most marked up-regulation, and was involved in many of the most important cellular response processes to the infection. There was dysregulation of apoptosis, tumor suppressor genes and oncogenes as early as in the first 24 h of H. pylori infection, which may represent early signs of gastric tumorigenesis. OMPLA⁺/⁻ did not affect the acute inflammatory response to H. pylori.
authors.affiliation: Department of Clinical Molecular Biology (Epigen), Institute of Clinical Medicine, University of Oslo, Akershus University Hospital, Lørenskog, Norway. lars.eftang@medisin.uio.no
authors.forename: Lars L
authors.initials: LL
authors.lastname: Eftang
authors.forename: Ying
authors.initials: Y
authors.lastname: Esbensen
authors.forename: Tone M
authors.initials: TM
authors.lastname: Tannæs
authors.forename: Ida R K
authors.initials: IR
authors.lastname: Bukholm
authors.forename: Geir
authors.initials: G
authors.lastname: Bukholm
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D046228:Microarray Analysis; D054466:Phospholipases A1 / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016209:Interleukin-8; D037521:Virulence Factors; D054466:Phospholipases A1; C412876:outer membrane phospholipase A