The Gastric Mucosa from Patients Infected with CagA+ or VacA+ Helicobacter pylori Has a Lower Level of Dual Oxidase-2 Expression than Uninfected or Infected with CagA-/VacA- H. pylori.

Abstract

BackgroundHelicobacter pylori (H. pylori) is a well-recognized gastroduodenal pathogen and class I carcinogen. Dual oxidase-2 (DUOX2), a member of NADPH oxidase family, has several critical physiological functions, including thyroid hormone biosynthesis and host mucosal defense.AimTo investigate the effect of H. pylori infection on DUOX2 gene expression in human stomach.Materials and MethodsThe biopsies were obtained from patients who underwent endoscopic diagnosis. The patient serum was assayed for two virulence factors of H. pylori, CagA IgG and VacA. The inflammation in gastric mucosa was analyzed with histology. Real-time quantitative PCR was used to detect the expression of three members of NADPH oxidase, NOX1, NOX2, and DUOX2, as well as lactoperoxidase (LPO) in the gastric mucosa. NOX2, DUOX2, and myeloperoxidase (MPO) protein levels were quantified by Western blots or immunohistochemistry.ResultsThe H. pylori-infected gastric mucosa had more severe inflammation than uninfected samples. However, the expression of DUOX2 mRNA and protein was lower in gastric mucosa of patients with H. pylori infection compared to the uninfected. Among the H. pylori-infected patients, those having CagA IgG or VacA in the serum had lower DUOX2 expression levels than those infected with H. pylori without either virulence factor. The NOX2 and MPO levels were higher in those patients infected with H. pylori irrespective of the virulence factors than those uninfected patients. NOX1 and LPO mRNA were undetectable in the gastric mucosa.ConclusionCagA+ or VacA+ H. pylori in the stomach of patients may suppress DUOX2 expression to promote its own survival. Increased NOX2 could not eliminate H. pylori infection.Electronic supplementary materialThe online version of this article (doi:10.1007/s10620-016-4144-z) contains supplementary material, which is available to authorized users.