Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. Pylori exposed gastric epithelial cells

Department of Clinical Molecular Biology (Epigen), Institute of Clinical Medicine, University of Oslo, Akershus University Hospital, Lørenskog, Norway.
BMC Microbiology (Impact Factor: 2.73). 01/2012; 12(1):9. DOI: 10.1186/1471-2180-12-9
Source: PubMed


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.
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.
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.

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    • "Similarly, in vitro co-culturing of H. pylori with gastric epithelial cells showed an increase in IL-8 secretion (Crabtree et al., 1995; Sharma et al., 1995). It was therefore no surprise that the whole genome profiling of H. pylori-infected gastric epithelial cells revealed IL-8 to be the most significantly upregulated gene (Eftang et al., 2012). IL-8 released by infected gastric epithelial cells is instrumental in regulating neutrophil infiltration of the gastric mucosa in H. pylori-associated gastritis (Nozawa et al., 2002). "
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    • "Both Pearson and Spearman correlation coefficients were employed to identify correlating genes. Among genes that correlated, we were particularly interested in those that showed a similar expression in our previously published study of H. pylori-exposed gastric epithelial cells [17]. The selected genes were then subjected to a Cox multivariate regression analysis to investigate whether any of the genes were independent predictors of post-operative survival in the GC patients, independent of histological type, tumor stage and size, nodal disease, and age at surgery. "
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    • "IL-8 plays a key role in promoting proliferation and survival of endothelial and cancer cells, angiogenesis and neutrophil infiltration [11,33]. IL-8 was the single most differentially expressed gene among 6000 significantly expressed genes in gastric epithelial cell line in response to Helicobacter pylori exposure [34]. Cooperation between AP-1 and NF-κB is required for optimal IL-8 gene induction in virus infected airway epithelium [35]. "
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