Effect of mannitol on Helicobacter pylori-induced cyclooxygenase-2 expression in gastric epithelial AGS cells.
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 F(1alpha) (6-keto-PGF(1alpha)) and thromboxane B(2) (TXB(2)) and H(2)O(2) were measured in the medium. The results showed that H. pylori induced H(2)O(2) production, COX-2 mRNA and protein expression and increased the levels of 6-keto-PGF(1alpha) and TXB(2). 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.
Kim
Hyeyoung
H
Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Kim626@yumc.yonsei.ac.kr
Seo
Jeong Yeon
JY
Kim
Kyung Hwan
KH
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004790:Enzyme Induction / Q000187:drug effects; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D007527:Isoenzymes; D008565:Membrane Proteins; D008353:Mannitol; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases