Effect of mannitol on helicobacter pylori-induced cyclooxygenase-2 expression in gastric epithelial AGS cells.

Abstract

Oxygen radicals have been considered to be important regulatory molecules in Helicobacter pylori-induced gastric ulceration and carcinogenesis. H. pylori-induced inflammation has been shown to be associated with cyclooxygenase-2 (COX-2) expression in experimental animals and human patients. This study aimed to determine if H. pylori produces oxygen radicals and induces COX-2 expression in gastric epithelial cells. A further aim was to resolve whether or not the H. pylori-induced COX-2 expression could be inhibited by mannitol, a known hydroxyl radical scavenger, and superoxide dismutase (SOD), an antioxidant enzyme, which was used as a positive control. A human gastric epithelial cell line, AGS, treated with or without mannitol or SOD, was incubated in the presence or absence of H. pylori. mRNA expression and protein levels for COX-2 were determined by Northern blot and Western blot analysis, respectively. Levels of the COX-2 products, 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) and H2O2 were measured in the medium. The results showed that H. pylori induced H2O2 production, COX-2 mRNA and protein expression and increased the levels of 6-keto-PGF1α and TXB2. The H. pylori-induced COX-2 expression and the increase in the COX-2 products were inhibited by both mannitol and SOD. The inhibitory effect of mannitol on H. pylori-induced COX-2 expression suggests the possible involvement of oxygen radicals in the transcriptional regulation of the inflammatory mediators in gastric epithelial cells.