Interferon gamma-signature transcript profiling and IL-23 upregulation in response to Helicobacter pylori infection

Unite de Pathogénie Bacterienne des Muqueuses, Institut Pasteur, Paris, France.
International journal of immunopathology and pharmacology (Impact Factor: 1.62). 07/2008; 21(3):515-26.
Source: PubMed


Helicobacter pylori infection is the major cause of gastroduodenal pathologies including gastric cancer. The long persistence of bacteria and the type of immune and inflammatory response determine the clinical issue. In this study, the global gene expression profile after 6 and 12 months of H. pylori infection was investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression Array A430. Genes related to the inflammatory and immune responses were focused. Levels of selected transcripts were confirmed by reverse transcription polymerase chain reaction. Twenty- five and nineteen percent of the differentially expressed genes observed at 6 and 12 months post-infection respectively, were related to immune response. They are characterized by an interferon (IFN)gamma-dependent expression associated to a T helper 1 (Th1) polarised response. In-depth analysis revealed that an up-regulation of IL-23p19, took place in the stomach of H. pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric biopsies from H. pylori-infected patients with chronic gastritis, as compared to healthy subjects. Our microarray analysis revealed also, a high decrease of H+K+-ATPase transcripts in the presence of the H. pylori infection. Association of gastric Th1 immune response with hypochlorhydria through the down-regulation of H+K+-ATPase contributes to the genesis of lesions upon the H. pylori infection. Our data highlight that the up-regulation of IL-23 and of many IFNgamma signature transcripts occur early on during the host response to H. pylori, and suggest that this type of immune response may promote the severity of the induced gastric lesions.

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Available from: Jose Ramos Vivas
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    • "High throughput microarray technology provides a powerful tool for comprehensive gene analysis, already applied to assess gene expression patterns in both human samples and animal models of gastric disorders [7-16]. Although many researchers have focused on gene expression in H. pylori-treated gastric cell lines [17-19], results in cell culture do not necessarily correlate with expression of specific genes in the in vivo microenvironment featuring host immune responses and stromal-epithelial interactions in cancers. "
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    • "Atypia in the antrum and the fundus are also observed. Consistent with our previous findings (Vivas et al., 2008), USF1 and USF2 gene expression levels were one-third to one half and one-sixth to one half those in uninfected mice at 12 and 18 months post infection respectively (Fig. 2B). H. pylori infection decreases USF1/USF2-DNA binding to the E-box promoter region USF1 and USF2 bind to the E-box element present in the promoter region of genes (Corre and Galibert, 2005). "
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    • "In H. pylori infection, a predominant activation of Th1 cells, with the production of IFN-g, IL-12, IL-18, IL-23 and TNFa , occurs in vivo in the stomach in human and animal models (Mohammadi et al., 1996; D'Elios et al., 1997; Luzza et al., 2000; Mattapallil et al., 2000; Rossi et al., 2000; Tomita et al., 2001; Vivas et al., 2008). Complex and fascinating mechanisms are responsible for the mucosal Th1 polarization (D'Elios et al., 1997, 2005; Del Giudice et al., 2001). "
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