Inducible nitric oxide synthase expression in helicobacter pylori CagA+ strains infections

ABSTRACT

Increased expression of inducible nitric oxide synthase [iNOS] has been observed in patients with chronic inflammatory diseases of the gastrointestinal tract leading to sustained production of nitric oxide [NO] which may induce DNA damage. Since Helicobacter pylori [H. pylori] infection produces a state of chronic immunostimmulation in the gastric epithelium and a causal relationship between H. pylori CagA+ strains infection and gastric cancer has been suggested, therefore, our aim was to evaluate the significance of iNOS expression in gastric lesions induced by H. pylori CagA+ strains with correlation to the encountered endoscopic and pathological diagnoses. Eighty four dyspeptic patients underwent endoscopic examination. Four antral gastric biopsies were obtained for detection of H. pylori by histopathological assessment [Giemsa staining], urease test and gene expression of H. pylori using PCR assay. Immunohistochemical staining for iNOS expression and quantitative detection of anti-CagA antibodies were performed. It was found that H. pylori infection was detected in 64.3%, CagA seropositivity in 54.8% and iNOS expression in 61.9%. Anti-CagA antibodies seropositivity and iNOS immunoexpression were significantly related to H. pylori infection. The positive rates of iNOS immunostaining increased with the lesion progression from chronic superficial gastritis to chronic atrophic gastritis to intestinal metaplasia [45.2%, 87.5% and 92.8% respectively]. Positive immunostaining rates of iNOS correlated significantly with H.pylori Cag A seropositivity with respect to both endoscopic and pathologic diagnoses. In conclusion, CagA+ H. pylori strains are associated with enhanced immunoexpression of iNOS in H. pylori-related gastric diseases, therefore they might contribute as risk cofactors that conduces to gastric carcinogenesis. Given the high prevalence of H. pylori gastric diseases and frequent performance level of endoscopic gastric examinations among Egyptian patients, prompt identification of gastric infections caused by H. pylori harboring Cag A virulence factor is necessary for the early eradication of infection before the development of pre-neoplastic lesions